Prenatal Exposure to Psychostimulants Increases Impulsivity, Compulsivity, and Motivation for Rewards in Adult Mice.

Prenatal exposure to psychostimulants increases impulsivity, compulsivity, and motivation for rewards in adult mice.

Physiol Behav. 2013 Jun 2;
Lloyd SA, Oltean C, Pass H, Phillips B, Staton K, Robertson CL, Shanks RA

Given the widespread use and misuse of methamphetamine (METH) and methylphenidate (MPD), especially in relation to women of childbearing age, it is important to consider the long-lasting effects of these drugs on the brain of the developing fetus. Male and female C57Bl/6J mice were prenatally exposed to METH (5mg/kg), MPD (10mg/kg), or saline. Following a 3-month washout, behavioral analysis using the 5-Choice Serial Reaction Time Task (5CSRTT) was performed on adult mice. After reaching training criteria, performance on a pseudo-random intertrial interval test session revealed decrements in 5CSRTT behavior. Prenatally-treated METH and MPD mice demonstrated significant increases in impulsivity, compulsivity, and motivation for reward compared to their saline controls. There were sex by drug interactions indicating a possible sexually dimorphic response to these prenatal drug exposures. Of particular clinical interest, we find that mice prenatally exposed to METH or MPD express characteristics of both inhibitory control decrements and heightened motivation for rewards, which represent core symptoms of addiction and other impulse control disorders. HubMed – addiction


High levels of intravenous mephedrone (4-methylmethcathinone) self-administration in rats: Neural consequences and comparison with methamphetamine.

J Psychopharmacol. 2013 Jun 5;
Motbey CP, Clemens KJ, Apetz N, Winstock AR, Ramsey J, Li KM, Wyatt N, Callaghan PD, Bowen MT, Cornish JL, McGregor IS

Mephedrone (MMC) is a relatively new recreational drug that has rapidly increased in popularity in recent years. This study explored the characteristics of intravenous MMC self-administration in the rat, with methamphetamine (METH) used as a comparator drug. Male Sprague-Dawley rats were trained to nose poke for intravenous MMC or METH in daily 2 h sessions over a 10 d acquisition period. Dose-response functions were then established under fixed- and progressive-ratio (FR and PR) schedules over three subsequent weeks of testing. Brains were analyzed ex vivo for striatal serotonin (5-HT) and dopamine (DA) levels and metabolites, while autoradiography assessed changes in the regional density of 5-HT and serotonin transporter (SERT) and DA transporter (DAT) and induction of the inflammation marker translocator protein (TSPO). Results showed that MMC was readily and vigorously self-administered via the intravenous route. Under a FR1 schedule, peak responding for MMC was obtained at 0.1 mg/kg/infusion, versus 0.01 mg/kg/infusion for METH. Break points under a PR schedule peaked at 1 mg/kg/infusion MMC versus 0.3 mg/kg/infusion for METH. Final intakes of MMC were 31.3 mg/kg/d compared to 4 mg/kg/d for METH. Rats self-administering MMC, but not METH, gained weight at a slower rate than control rats. METH, but not MMC, self-administration elevated TSPO receptor density in the nucleus accumbens and hippocampus, while MMC, but not METH, self-administration decreased striatal 5-hydroxyindolacetic acid (5-HIAA) concentrations. In summary, MMC supported high levels of self-administration, matching or exceeding those previously reported with other drugs of abuse. HubMed – addiction


Acute and chronic effects of alcohol on trail making test performance among underage drinkers in a field setting.

J Stud Alcohol Drugs. 2013 Jul; 74(4): 635-41
Day AM, Celio MA, Lisman SA, Johansen GE, Spear LP

ABSTRACT. Objective: Alcohol’s effects on executive functioning are well documented. Research in this area has provided much information on both the acute and chronic effects of alcohol on processes such as working memory and mental flexibility. However, most research on the acute effects of alcohol is conducted with individuals older than 21 years of age. Using field recruitment methods can provide unique empirical data on the acute effects of alcohol on an underage population. Method: The current study examined the independent effects of acute alcohol intoxication (measured by breath alcohol content) and chronic alcohol use (measured by years drinking) on a test of visuomotor performance and mental flexibility (Trail Making Test) among 91 drinkers ages 18-20 years recruited from a field setting. Results: Results show that breath alcohol predicts performance on Trails B, but not on Trails A, and that years drinking, above and beyond acute intoxication, predicts poorer performance on both Trails A and B. Conclusions: These data suggest that, independent of the acute effects of alcohol, chronic alcohol consumption has deleterious effects on executive functioning processes among underage drinkers. Our discussion focuses on the importance of these data in describing the effect of alcohol on adolescents and the potential for engaging in risky behavior while intoxicated. (J. Stud. Alcohol Drugs, 74, 635-641, 2013). HubMed – addiction