Ryan A. Shanks

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

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.

Adolescent exposure to cocaine, amphetamine, and methylphenidate cross-sensitizes adults to methamphetamine with drug- and sex-specific effects.

The increasing availability, over-prescription, and misuse and abuse of ADHD psychostimulant medications in adolescent populations necessitates studies investigating the long-term effects of these drugs persisting into adulthood. Male and female C57Bl/6J mice were exposed to amphetamine (AMPH) (1.0 and 10 mg/kg), methylphenidate (MPD) (1.0 and 10 mg/kg), or cocaine (COC) (5.0 mg/kg) from postnatal day 22 to 31, which represents an early adolescent period. After an extended period of drug abstinence, adult mice were challenged with a subacute methamphetamine (METH) dose (0.5 mg/kg), to test the long-term effects of adolescent drug exposures on behavioral cross-sensitization using an open field chamber. There were no sex- or dose-specific effects on motor activity in adolescent, saline-treated controls. However, AMPH, MPD, and COC adolescent exposures induced cross-sensitization to a subacute METH dose in adulthood, which is a hallmark of addiction and a marker of long-lasting plastic changes in the brain. Of additional clinical importance, AMPH-exposed male mice demonstrated increased cross-sensitization to METH in contrast to the female-specific response observed in MPD-treated animals. There were no sex-specific effects after adolescent COC exposures. This study demonstrates differential drug, dose, and sex-specific alterations induced by early adolescent psychostimulant exposure, which leads to behavioral alterations that persist into adulthood.

Chronic methamphetamine exposure significantly decreases microglia activation in the arcuate nucleus

Methamphetamine is a powerful psychostimulant drug and its use and abuse necessitates a better understanding of its neurobiobehavioral effects. The acute effects of binge dosing of methamphetamine on the neurons in the CNS are well studied. However, the long-term effects of chronic, low-dose methamphetamine are less well characterized, especially in other cell types and areas outside of the major dopamine pathways. Mice were administered 5mg/kg/day methamphetamine for ten days and brain tissue was analyzed using histochemistry and image analysis. Increased microglia activity in the striatum confirmed toxic effects of methamphetamine in this brain region using this dosing paradigm. A significant decrease in microglia activity in the arcuate nucleus of the hypothalamus was observed with no effect noted on dopamine neurons in the arcuate nucleus. Given the importance of this area in homeostatic and neuroendocrine regulation, the current study highlights the need to more fully understand the systemic effects of chronic, low-dose methamphetamine use. The novel finding of microglia downregulation after chronic methamphetamine could lead to advances in understanding neuroinflammatory responses towards addiction treatment and protection from psychostimulant-induced neurotoxicity.

Measuring and Advancing Experimental Design Ability in an Introductory Course without Altering Existing Lab Curriculum

Introductory biology courses provide an important opportunity to prepare students for future courses, yet existing cookbook labs, although important in their own way, fail to provide many of the advantages of semester-long research experiences. Engaging, authentic research experiences aid biology students in meeting many learning goals. Therefore, overlaying a research experience onto the existing lab structure allows faculty to overcome barriers involving curricular change. Here we propose a working model for this overlay design in an introductory biology course and detail a means to conduct this lab with minimal increases in student and faculty workloads. Furthermore, we conducted exploratory factor analysis of the Experimental Design Ability Test (EDAT) and uncovered two latent factors which provide valid means to assess this overlay model’s ability to increase advanced experimental design abilities. In a pre-test/post-test design, we demonstrate significant increases in both basic and advanced experimental design abilities in an experimental and comparison group. We measured significantly higher gains in advanced experimental design understanding in students in the experimental group. We believe this overlay model and EDAT factor analysis contribute a novel means to conduct and assess the effectiveness of authentic research experiences in an introductory course without major changes to the course curriculum and with minimal increases in faculty and student workloads.

Of Mice and Meth: A New Media-Based Neuropsychopharmacology Lab to Teach Research Methods

This article describes an innovative neuropsychopharmacology laboratory that can be incorporated into any research methods class. The lab consists of a set of interconnected modules centered on observations of methamphetamine-induced behavioral changes in mice and is designed to provide students with an opportunity to acquire basic skills necessary for conducting research. To assess the practical utility of this new laboratory, an empirical study was conducted to determine whether different formats of the lab produce similar learning gains. The results suggest that both the live and the media-based variations of this lab are similarly effective. Thus, to facilitate the adoption of the lab, especially in its media-based format, all necessary materials are made available on a dedicated website.