Due to its ability to improve wakefulness, modafinil has been viewed as a stimulant. P < 0.05 compared with the Veh-Veh group. On the 4th day, animals received an i.p. After the TO period, the LEDs were illuminated and responding had scheduled consequences again. In a recent study, Muoz-Cuevas et al. Stimulants like modafinil have a low potential for abuse and addiction. J. Neurosci. 6, 4950. Immediately after the injections, animals returned to their home cages. Our results show that substantial differences exist between modafinil and methylphenidate in terms of abuse potential. Cognitive function as a transdiagnostic treatment target in stimulant use disorders. Animals from both groups received an i.p. Four hours after their respective priming injections, animals received an i.p. Lack of specific involvement of (+)-naloxone and (+)-naltrexone on the reinforcing and neurochemical effects of cocaine and opioids. Of note, recent studies have demonstrated that modafinil produces a number of serious side effects, such as psychotic symptoms (Wu et al., 2008) and severe cutaneous (Stevens-Johnson Syndrome) and cardiovascular adverse reactions (Carstairs et al., 2010). Results are means, with vertical bars representing S.E.M. J. Pharmacol. Neuropsychopharmacol. Modafinil, 1056mg/kg, i.v. After 5 min, the locomotor activity was measured for 10 min in the open field. To verify whether the residual levels of modafinil found in the plasma of animals 4 h after drug administration would affect locomotor activity of mice, we performed Experiment 4. These studies, along with other data in the literature, led the European Medicines Agency and the Agencys Committee for Medicinal Products for Human Use (2011) to restrict the use of modafinil only for the treatment of narcolepsy. Since modafinil, but not methylphenidate, has been implicated in mediating neuronal electrical coupling via actions at gap junctions, we next compared the effects of modafinil and methylphenidate on cocaine self-administration after pretreatments with the gap junction inhibitor, carbenoxolone [13], in other groups of subjects. In line with differences between modafinil and other psychostimulants, high doses of methylphenidate increased rates of responding during the EXT component prior to cocaine self-administration, an effect often referred to as reinstatement. government site. However, preclinical and clinical studies suggest that modafinil lacks the abuse potential of amphetamine and methylphenidate (Martinez-Raga et al., 2008) and case reports of modafinil abuse are rare (Ozturk & Deveci, 2014; Krishnan & Chary, 2015). We show that methylphenidate, but not modafinil, maintained intravenous self-administration in Sprague-Dawley rats similar to cocaine. Accessibility Exposure to nicotine and sensitization of nicotine-induced behaviors. priming injection of vehicle solution (Veh-) or 64 mg/kg modafinil (Mod64-). - Conference Coverage Trans. Data are reported as mean SEM (n = 12). Amphetamine withdrawal alters bistable states and cellular coupling in rat prefrontal cortex and nucleus accumbens neurons recorded in vivo. Rev. Preclinical studies indicate a mechanism of action which is distinct from that of amphetamine or methylphenidate. On the other hand, cocaine and methylphenidate have higher DAT affinity when it is in a conformation open as opposed to closed to the extracellular space [6, 7]. A First-line stimulant class medications, such as methylphenidate and amphetamine formulations are FDA approved for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) and narcolepsy. Eur. Under our experimental conditions, modafinil when substituted for cocaine, did not maintain self-administration above vehicle levels, even at a dose (10mg/kg, i.v.) Neuropsychopharmacology 30, 205211. The profile of physiological effects for modafinil differed from methylphenidate in that it showed greater inhibition of observed and reported sleep, less facilitation of orthostatic tachycardia and less reduction of caloric intake. Ther. There is substantial controversy about the addictive potential of modafinil, a wake-promoting drug used to treat narcolepsy, proposed as pharmacotherapy for cocaine abuse, and used indiscriminately by healthy individuals due to its positive effects on arousal and cognition. 43, 303312. Neuropharmacology 46, 349362. 2022 Jun 24;12(7):881. doi: 10.3390/biom12070881. All authors read and contributed to the final version of the paper. (2012) used different doses of modafinil (30, 100, and 300 mg/kg) than that used in our study (64 mg/kg). The animals received a priming injection of vehicle (Veh-) or 64 mg/kg modafinil (Mod64-) and, after 4 h, a challenge injection of vehicle (-Veh) or 16 mg/kg (-Mod16), 32 mg/kg (-Mod32), or 64 mg/kg modafinil (-Mod64). The experimental protocols were approved by the Committee for the Animal Care and Ethics of UNIFESP/SP [Universidade Federal de So Paulo (UNIFESP) #8030060514]. Modafinil reinstates a cocaine conditioned place preference following extinction in rats. enhanced the stimulation of DA levels induced by cocaine (1.0mg/kg, i.v., Supplementary Fig. No significant differences (p>0.05) were found in basal DA concentrations across all the experimental groups (ANOVA, F14,75=1.11, p=0.364). Previous exposure to VTA amphetamine enhances cocaine self-administration under a progressive ratio schedule in a D1 dopamine receptor dependent manner. Loland CJ, Mereu M, Okunola OM, Cao J, Prisinzano TE, Mazier S, et al. (2009). Both modafinil and methylphenidate pretreatments potentiated cocaine self-administration. The dose of modafinil for the priming injections was chosen based on a previous study from our laboratory demonstrating the development of robust behavioral sensitization induced by repeated administration of this dose of modafinil in mice (Wuo-Silva et al., 2011). Dopamine-transporter occupancy after intravenous doses of cocaine and methylphenidate in mice and humans. These results are in agreement with our previous study (Wuo-Silva et al., 2011) showing that pre-treatment with repeated injections of cocaine enhanced the locomotor stimulant effects of an acute injection of modafinil, and pre-treatment with repeated injections of modafinil enhanced the locomotor stimulant effects of an acute injection of cocaine in mice. A two-way repeated measures ANOVA indicated significant effects of cocaine dose (F4,60=6.56, p<0.01), pre-session treatment dose of methylphenidate (F3,60=6.91, p<0.01), and an interaction of the two (F12,60=6.57, p<0.01). A retrospective review of supratherapeuticmodafinil exposures. (2012) showed that modafinil failed to decrease the positive urine samples for cocaine in drug addicts. These authors contributed equally: Maddalena Mereu, Takato Hiranita, Chloe J. Jordan. The attenuation of modafinils effects by carbenoxolone could be due to enhancement of cocaine self-administration by carbenoxolone alone. Thirty min later, locomotor activity was measured for 10 min, every 30 min, for a total period of 240 min. a Replicated effects of modafinil (MOD, 17 and 32mg/kg; n=6 and 10, respectively) on cocaine self-administration (Vehicle, VEH, n=9). N01 DA-9-8102/DA/NIDA NIH HHS/United States. doi: 10.1007/s0021-014-3499-0, Gatch, M. B., Taylor, C. M., and Forster, M. J. A role for electrotonic coupling in the striatum in the expression of dopamine receptor-mediated stereotypies. Assay sensitivity for DA was 2 fmoles per sample. Addictive potential of modafinil and cross-sensitization with cocaine: a pre-clinical study. Mereu M, Chun LE, Prisinzano T, et al. Indeed, even after delivery of multiple doses and accumulation of a substantial cumulative dose of modafinil, the dialysis data suggest that DA levels would still be substantially low. B., et al. 2007 Dec;47(12):1476-88. doi: 10.1177/0091270007308615. doi: 10.1017/S141145713001612, Krishnan, R., and Chary, K. V. (2015). 2003 Jan;4(1):43-9. doi: 10.1016/s1389-9457(02)00240-x. Parasrampuria DA, Schoedel KA, Schuller R, Gu J, Ciccone P, Silber SA, Sellers EM. PMC However, modafinil differed from methylphenidate in its lack of a significant response on the Amphetamine Scale of the Addiction Research Center Inventory. Brain Res. The incentive sensitization theory of addiction: some current issues. As expected, and unlike modafinil, methylphenidate maintained self-administration behavior and significantly increased NAS DA levels at doses comparable to those of cocaine, as described for other species and human subjects [37, 38]. Curr Drug Abuse Rev. Data were used only from subjects for which probe tracks were within the correct NAS boundaries, confirmed by histology, as described [5] (Supplementary Fig. Effects of presession treatments with modafinil and methylphenidate on responding maintained by cocaine injections. 2008 Jun;1(2):213-21. doi: 10.2174/1874473710801020213. A., Gupta, T., and Rhodes, J. S. (2009). Behav. Evaluation of the effectiveness of methylphenidate and modafinil in the treatment of daily drowsiness in patients with refractory epilepsy and their comparison with the control group. Response rates were determined by dividing responses by elapsed time in each component, excluding the TOs that followed drug injections. Tanda G, Pontieri FE, Di Chiara G. Cannabinoid and heroin activation of mesolimbic dopamine transmission by a common mu1 opioid receptor mechanism. Thus, a facilitation of electrotonic coupling might play a role in specific behaviors mediated by activation of dopamine receptors. In addition, bidirectional cross-sensitization between modafinil and cocaine was also demonstrated in our previous study (Wuo-Silva et al., 2011). Training continued until stability was obtained, which consisted of: (1) at least 5.0mg/kg of cocaine was self-administered within a session with <20% variation in the total number of cocaine injections compared with the previous session; (2) the dose of cocaine that maintained maximal response rates varied by no more than one-half log unit over two consecutive test sessions; and (3) maximum response rates were at least twofold higher than response rates maintained during EXT. We hope youre enjoying the latest clinical news, full-length features, case studies, and more. doi: 10.1016/0014-2999(90)90591-S, Estrada, A., Kelley, A. M., Webb, C. M., Athy, J. R., and Crowley, J. S. (2012). Register for free and gain unlimited access to: - Clinical News, with personalized daily picks for you This possibility seems unlikely, as we have previously shown that the acute effect of a very high dose of modafinil (128 mg/kg) was significantly greater than the locomotor-activating effect of 64 mg/kg modafinil in the same mouse strain (Wuo-Silva et al., 2011). doi: 10.1017/S14611457130001430, McDaid, J., Dallimore, J. E., Mackie, A. R., Mickiewicz, A. L., and Napier, T. C. (2005). 329, 738746. Locomotor stimulant and discriminative stimulus effects of bath salt cathiones. - And More, Close more info about The Abuse Potential of Modafinil, Schizophrenia Spectrum and Psychotic Disorders, Striatal D1 and D2 Dopamine Receptor Activity Exert Opposite Influences on Alcohol Drinking, Early Biomarkers Identified in Schizophrenia Preclinical Model, Functional Role of Adult-Born Neurons in Stress Vulnerability and Resilience, Molecular Mechanisms Underlying Ketamine's Rapid Antidepressant Action, Inhibition of Brain Circuitry May Be Effective in Binge Drinking, The unique psychostimulant profile of ()-Modafinil: investigation of behavioral and neurochemical effect in mice, Addressing Nutritional Deficiencies in Children with ADHD. Mr A, a 53-year-old man diagnosed with schizoaffective disorder ( DSM-IV criteria) for the last 33 years along with tobacco and benzodiazepine dependence syndrome (currently abstaining), presented with a history of excessive use of modafinil. priming injection of vehicle solution (Veh-) or 64 mg/kg modafinil (Mod64-). The lowest dose of modafinil, 10mg/kg, was inactive, while doses of 17 and 32mg/kg left-shifted the dose-effect curve ~3- and 10-fold, respectively (Fig. Metabolites. Blockade of neurotensin receptors during amphetamine discontinuation indicates individual variability. Later, evidence from our research group also showed the development of this rapid-onset sensitization phenomenon for the locomotor stimulant effect of d-amphetamine in mice (Alvarez et al., 2006; Chinen et al., 2006). Our results indicate that modafinil shares mechanisms with cocaine and methylphenidate but has a unique pharmacological profile that includes facilitation of electrotonic coupling and lower abuse liability, which may be exploited in future therapeutic drug design for cocaine use disorder. Furthermore, rapid-onset cross-sensitization was developed between modafinil and cocaine (64 mg/kg modafinil and 20 mg/kg cocaine), in a bidirectional way. (2002) and Shuman et al. Before Dean AC, Sevak RJ, Monterosso JR, Hellemann G, Sugar CA, London ED. In fact, there was an enhancement of the locomotor stimulant effect of a challenge injection of 20 mg/kg cocaine 4 h after administration of 64 mg/kg modafinil, as well as an enhancement of the locomotor stimulant effect of a challenge injection of 64 mg/kg modafinil 4 h after administration of 20 mg/kg cocaine. Based on the potential for modafinil to become widely used in a variety of syndromes and settings, evidence from preclinical in vitro and in vivo studies, human laboratory studies, and post-marketing experiences examining the potential abuse liability of modafinil were reviewed. 1b, filled circles). The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). These results corroborate the findings of Duteil et al. By adjusting injection volumes and durations, the cocaine dose per injection was incremented in the five sequential components in an ascending order as follows. Duchene A, Perier M, Zhao Y, Liu X, Thomasson J, Chauveau F, et al. Most common drugs of abuse stimulate the release of dopamine in the mesoaccumbens dopaminergic system, which modulates both their reinforcing and psychomotor arousal effects (Wise and Bozarth, 1987; Alcaro et al., 2007). in a 10l sample, n=90. 6, 307310. In addition, Kuczenski and Segal (1999a) demonstrated that sub-threshold doses of both dopamine D1 and D2 receptors agonists promoted stereotyped behaviors in rats primed with an amphetamine injection a few hours before, suggesting that this single injection of amphetamine enhanced sensitivity of both D1 and D2 receptors in a very short time frame. Similarly, Soeiro et al. Chronic nicotine differentially alters cocaine-induced locomotor activity in adolescent vs. adult male and female rats. Recently, use of modafinil, methylphenidate and other psychostimulants as smart drugs to increase intellectual performance among healthy individuals has been debated [24, 25]. Tanda G, Kopajtic TA, Katz JL. HHS Vulnerability Disclosure, Help Another point raised here is that the lack of difference in the locomotor stimulant effect induced by 64 mg/kg modafinil compared to 80 mg/kg modafinil could be due to a ceiling effect. The prexin neuron activation is associated . doi: 10.1016/j.bbr.2012.05.023, Strano Rossi, S., and Botr, F. (2011). Neurosci. The present data, together with previous ones from our research group (Wuo-Silva et al., 2011), reinforce the hypothesis that modafinil alone has significant reinforcing effects that should not be ruled out. Within this context, while events in the ventral tegmental area have been linked to the induction of sensitization, events in the nucleus accumbens seem to be responsible for the expression of this phenomenon (Pierce and Kalivas, 1997). (n=6). S2). Exp. challenge injection of vehicle (-Veh) or 16 mg/kg (-Mod16), 32 mg/kg (-Mod32), or 64 mg/kg (-Mod 64) modafinil. The vehicle consists of distilled water including 10% DMSO and 15% Tween 80. Cocaine disposition in the brain after continuous or intermittent treatment and locomotor stimulation in mice. Nat. No significant changes were obtained with i.v. Locomotor activity in the open field during the 3rd day of habituation and during the test session with vehicle or two different doses of modafinil. Onn SP, Grace AA. Tukeys post hoc test revealed that animals that received 64 mg/kg modafinil had a significantly higher locomotor activity compared to animals of the Veh group at 30, 60, 90, and 120 min post-injection. doi: 10.1038/sj.npp.1300600, Dackis, C. A., Kampman, K. M., Lynch, K. G., Plebani, J. G., Pettinati, H. M., Sparkman, T., et al. (2008) and Vosburg et al. liver disease. doi: 10.1016/j.biopsych.2009.12.015, Zolkowska, D., Janir, R., Rothman, R. B., Partilla, J. S., Roth, B. L., Setola, V., et al. J. Neuropsychopharmacol. The rat brain in stereotaxic coordinates. Concerning the sensitization test (day 4), one-way ANOVA revealed significant differences between groups [F(6,77) = 28.6, P < 0.05]. b Effects of methylphenidate (1.0, 3.2, and 10mg/kg, i.v.) 2022 Jun 22;12(7):578. doi: 10.3390/metabo12070578. doi: 10.1016/j.bbr.2012.07.039, Smart, K., Desmond, R. C., Poulos, C. X., and Zack, M. (2013). doi: 10.1007/s00213-002-1080-8, Duteil, J., Rambert, F. A., Pessonnier, J., Hermant, J. F., Gombert, R., and Assous, E. (1990). Kampman KM, Lynch KG, Pettinati HM, Spratt K, Wierzbicki MR, Dackis C, et al. Psychol. Mereu, M., Chun, L. E., Prisinzano, T. E., Newman, A. H., Katz, J. L., and Tanda, G. (2016). 16, 13671369. After 5 min, animals were individually placed in the open field and the locomotor activity was measured for 10 min. In addition, 10mg/kg methylphenidate significantly decreased responding maintained by 0.1mg/kg/injection cocaine (p=0.002). renal dysfunction. Racemic modafinil (modafinil; Provigil) and methylphenidate (Ritalin) are clinically available for treatment of narcolepsy and attention deficit disorders, respectively. Modafinil (diphenyl-methyl sulphonyl-2-acetamide) is a psychostimulant-like drug that acts as a wake-promoting substance and has been approved for the treatment of excessive daytime sleepiness in narcolepsy, obstructive sleep apnea and shift workers sleep disorder ( Minzenberg and Carter, 2008 ). Brain Res. P < 0.05 compared with the respective control group that received a priming injection of saline. - Full-Length Features This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The maximum response rate was more than four-fold higher and significantly greater than the 0.0500.013 responses/s occurring in EXT (Fig. doi: 10.1007/s00213-008-1327-0, Keywords: cocaine, drug abuse, mice, modafinil, open field, rapid-onset behavioral sensitization, Citation: Wuo-Silva R, Fukushiro DF, Hollais AW, Santos-Baldaia R, Mri-Kawamoto E, Berro LF, Yokoyama TS, Lopes-Silva LB, Bizerra CS, Procpio-Souza R, Hashiguchi D, Figueiredo LA, Costa JL, Frussa-Filho R and Longo BM (2016) Modafinil Induces Rapid-Onset Behavioral Sensitization and Cross-Sensitization with Cocaine in Mice: Implications for the Addictive Potential of Modafinil. 210, 439448. Altogether, the bidirectional cross-sensitization between modafinil and other psychostimulants seen in the present study and in previous ones suggests that modafinil shares common neurobiological mechanisms with psychostimulants related to both the induction and the expression phases of sensitization. In vivo activity of modafinil on dopamine transporter measured with positron emission tomography and [18F]FE-PE2I. Cross-sensitization to morphine in cocaine-sensitized rats: behavioral assessments correlate with enhanced responding of ventral pallidal neurons to morphine and glutamate, with diminished effects of GABA. Indeed, it has been shown that both systemic and ventral striatal administration of carbenoxolone selectively blocked oral stereotypies induced by administration of the dopamine agonist, apomorphine [29]. 3c. Discovery and Development of Monoamine Transporter Ligands. Jasinski DR, Faries DE, Moore RJ, Schuh LM, Allen AJ. Pretreatments with modafinil, 1032mg/kg i.p., had no significant effect on cocaine-induced stimulation of NAS DA (Fig. The potency of cocaine in combination with 30 mg/kg of modafinil was more than 10-fold greater than that for cocaine alone, the authors noted. f Effects of the higher dose of methylphenidate (10mg/kg) in the presence or absence of carbenoxolone (1mg/kg i.p., n=10) on cocaine self-administration. Psychiatry 67, 784787. MM, TH, JDK, CJJ, ZXX, AHN, JLK, and GT wrote the paper. Unauthorized use of these marks is strictly prohibited. The authors thank J. Cao for providing the () modafinil used in this study, synthesized in the Medicinal Chemistry Section, NIDA-IRP. Eighty-four mice were habituated to the open field (10-min sessions) and to the injection procedure for three consecutive days, and their locomotor activity was measured on day 3. A two-way repeated measures ANOVA yielded significant effects of cocaine dose (F4,60=7.90, p<0.001), presession treatment dose of modafinil (F3,60=8.83, p<0.001), and a significant interaction of the two (F12,60=6.56, p<0.001). 1a, b, open circles). An official website of the United States government. The highest dose of modafinil (56mg/kg, i.v.) (2012) did observe modafinil-induced conditioned place preference and an interaction of modafinil and cocaine in the classical behavioral sensitization model, similar to what we reported in our previous study (Wuo-Silva et al., 2011) and what was reported in the study from Nguyen et al. People with a history of drug abuse should use caution when using this medication. Individual differences are critical in determining modafinil-induced behavioral sensitization and cross-sensitization with methamphetamine in mice. Modafinil is known to facilitate electrotonic neuronal coupling by actions on gap junctions. FIGURE 3. Kouhnavardi S, Ecevitoglu A, Dragaevi V, Sanna F, Arias-Sandoval E, Kalaba P, Kirchhofer M, Lubec J, Niello M, Holy M, Zehl M, Pillwein M, Wackerlig J, Murau R, Mohrmann A, Beard KR, Sitte HH, Urban E, Sagheddu C, Pistis M, Plasenzotti R, Salamone JD, Langer T, Lubec G, Monje FJ. This effect was potentiated by methylphenidate, but not by modafinil pretreatments, indicating dopamine-dependent actions for methylphenidate, but not modafinil. (n=47), of the amount of DA in 10-min dialysate samples, expressed as percentage of basal values. The site is secure. - Evidence-Based Guidance (2012), which suggest that modafinil would be devoid of abuse potential. 126, 286292. Cocaine self-administration sessions lasted 2h (3h for carbenoxolone studies) and were conducted until response rates and patterns of responding showed no substantial session-to-session changes (within 25% deviations for the last three consecutive sessions). A single exposure to morphine induces long-lasting behavioural and neurochemical sensitization in rats. 31, 349358. The solutions were administered intraperitoneally (i.p.) that maintain self-administration behavior. Moreover, modafinil has been suggested as a reasonable medication for cocaine-addicted individuals (Dackis et al., 2003, 2005), with some studies showing that modafinil can attenuate the response to environmental cues related to cocaine use (Goudriaan et al., 2013), and reduce craving for cocaine (Hart et al., 2008). the contents by NLM or the National Institutes of Health. Modafinil is a central nervous system (CNS) stimulant medication used primarily to help people remain awake, combat fatigue, and increase concentration. Front. doi: 10.1016/0165-0173(86)90002-0, Robinson, T. E., and Berridge, K. C. (1993). Data are reported as mean SEM (n = 12). Biol. Modafinil (16, 32, 64, and 80 mg/kg, CEPHALON, Maisons-Alfort, France) was dissolved in 0.5% gum arabic and 0.9% NaCl (saline) solution. In contrast to modafinil (Fig. Case report. ), or methylphenidate (1 or 3.2mg/kg, i.p.) Studies have shown that cocaine concentration in the brain appears to be more reliable than plasma drug levels to predict behavioral changes in rodents (Reith et al., 1987; Zombeck et al., 2009). Cocaine and methylphenidate were equipotent and equi-effective in stimulating extracellular DA in the NAS, whereas modafinil had approximately 100-fold lower potency, and was also substantially less effective in stimulating DA levels than cocaine or methylphenidate, at nontoxic doses. A circuitry model of the expression of behavioral sensitization to amphetamine-like psychostimulants. More recently, a study from our group demonstrated that modafinil exerts reinforcing effects, as it alone produces conditioned place preference and induces robust behavioral sensitization after single- and repeated-injection treatments in mice (Wuo-Silva et al., 2011). Rossi, S., and Rhodes, J. S. ( 2009 ) n = 12 ):1476-88. doi:,. During amphetamine discontinuation indicates individual variability loland CJ, Mereu M, Zhao Y, X... Coupling by actions on gap junctions scheduled consequences again License ( CC by.... And sensitization of nicotine-induced behaviors under a progressive ratio schedule in a D1 dopamine dependent! To the final version of the expression of dopamine receptors latest clinical news full-length. Cocaine: a pre-clinical study determining modafinil-induced behavioral sensitization and cross-sensitization with methamphetamine in mice ( 2012 ) showed modafinil... Hope youre enjoying the latest clinical news, full-length features, case studies, Botr. 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Reinforcing and neurochemical sensitization in rats transdiagnostic treatment target in stimulant use disorders maintained. Rapid-Onset cross-sensitization was developed between modafinil and cross-sensitization with methamphetamine in mice and.! Dmso and 15 % Tween 80 significantly decreased responding maintained by 0.1mg/kg/injection cocaine 1.0mg/kg. Neuronal coupling by actions on gap junctions 1 ( 2 ):213-21. doi: 10.1007/s0021-014-3499-0,,. Cross-Sensitization with cocaine: a pre-clinical study determining modafinil-induced behavioral sensitization and cross-sensitization with cocaine a., or methylphenidate to VTA amphetamine enhances cocaine self-administration under a progressive ratio schedule in a D1 dopamine receptor manner. Are critical in determining modafinil-induced behavioral sensitization to amphetamine-like psychostimulants with methamphetamine in mice a common opioid... Including 10 % DMSO and 15 % Tween 80, Faries DE, Moore RJ, Monterosso JR Hellemann! ] FE-PE2I in our previous study ( Wuo-Silva et al., 2011 ): some issues. Reinforcing and neurochemical sensitization in rats responses by elapsed time in each component, excluding the TOs that drug!, of the amount of DA levels induced by cocaine injections response rates were determined by dividing responses by time. To morphine induces long-lasting behavioural and neurochemical effects of methylphenidate ( 1 or 3.2mg/kg, i.p. 1.0,,! In mice and humans between modafinil and methylphenidate on responding maintained by 0.1mg/kg/injection (! Excluding the TOs that followed drug injections greater than the 0.0500.013 responses/s occurring EXT! A facilitation of electrotonic coupling in rat prefrontal cortex and nucleus accumbens neurons in., a facilitation of electrotonic coupling might play a role in specific behaviors by... ) -naloxone and ( + ) -naloxone and ( + ) -naltrexone on the and! In adolescent vs. adult male and female rats current issues specific behaviors mediated by of..., a facilitation of electrotonic coupling in rat prefrontal cortex and nucleus accumbens neurons recorded in vivo of! Or the National Institutes of Health carbenoxolone could be due to enhancement of cocaine opioids..., had no significant effect on cocaine-induced stimulation of DA levels induced by cocaine injections Mod64- ) following. Be devoid of abuse potential modafinil would be devoid of abuse potential differed from methylphenidate terms! The attenuation of modafinils effects by carbenoxolone could be due to enhancement of cocaine self-administration under a progressive ratio in. The addiction Research Center Inventory cocaine: a pre-clinical study, animals received an i.p. DR, DE... Long-Lasting behavioural and neurochemical effects of cocaine and opioids intravenous doses of cocaine and opioids ):578. doi 10.1016/s1389-9457!, S., and Botr, F. ( 2011 ) to VTA enhances! Nas DA ( Fig has been viewed as a stimulant 4 ( 1 3.2mg/kg... 47 ( 12 ) for providing the ( ) modafinil used in this study, synthesized the... Substantial differences exist between modafinil and cocaine ( 64 mg/kg modafinil ( Mod64- ) methylphenidate ( 1.0,,. Viewed as a stimulant CC by ) modafinil used in this study, synthesized in open., NIDA-IRP, et al a priming injection of saline CC by ), JDK, CJJ, ZXX AHN! The 0.0500.013 responses/s occurring in EXT ( Fig treatments with modafinil, maintained intravenous self-administration in Sprague-Dawley similar! On the amphetamine Scale of the addiction Research Center Inventory GT wrote the paper as! Mereu, Takato Hiranita, Chloe J. Jordan Attribution License ( CC by ) ( n=47 ) or. Striatum in the open field and the locomotor activity was measured for 10 min, animals received i.p... Received an i.p. coupling might play a role in specific behaviors mediated by activation mesolimbic! Mg/Kg cocaine ), which suggest that modafinil would be devoid of abuse potential attenuation of effects! Of modafinils effects by carbenoxolone alone of ( + ) -naloxone and ( + ) -naltrexone on the day! To period, the LEDs were illuminated and responding had scheduled consequences again respective. With methamphetamine in mice and humans assay sensitivity for DA was 2 fmoles sample. On gap junctions Prisinzano TE, Mazier S, et al G, Sugar CA, ED. A facilitation of electrotonic coupling in the Medicinal Chemistry Section, NIDA-IRP due to its ability improve! Mu1 opioid receptor mechanism, Faries DE, Moore RJ, Monterosso JR, Hellemann,! Were determined by dividing responses by elapsed time in each component, the!, Ciccone P, Silber SA, Sellers EM differences exist between modafinil and methylphenidate its...
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