Labratory Research
Self-Administration of Psychomotor Stimulants
In order to examine the acute and long-term effects of drug exposure during various stages of postnatal development, we use mainly the operant behavior model of intravenous drug self-administration in rats. We are interested in differential drug effects between genders, so both males and females are tested in most of our experiments. The overall goal is to explore the ontological development of reinforcement, as well as the social and physiological factors influencing drug use and effects in developing rats. Drugs of interest in the psychomotor stimulant class include cocaine, amphetamine, nicotine, caffeine, and MDMA (ecstasy). Specific projects are described below.
- Nucleus Accumbens Efferents in Reward and Reinforcement: A large literature attests to the crucial involvement of the ventral forebrain nucleus accumbens in reward and reinforcement. Although quite a bit is known about the roles of afferents to the accumbens, relatively little is known of accumbal efferents which may carry the “reward signal” to the rest of the brain. Thus, in collaboration with Dr. Darryl Neill in Emory University’s Department of Psychology, are testing the hypothesis that GABAergic projections from the nucleus accumbens to the ventral pallidum (VP) or the substantia nigra pars reticulate (SNpr) carries the “reward signal”. We are testing in three different behavioral paradigms: intra-cranial amphetamine self-administration, intra-cranial self-stimulation (electrical stimulation in the Neill laboratory), and food self-administration.
- Amphetamine Self-Administration in Periadolescent vs. Adult Rats: Data regarding differential responsivity to psychomotor stimulants among adolescent vs. adult subjects have been mixed. Some reports suggest a periadolescent hyposensitivity to psychomotor stimulants such as cocaine and amphetamine in motor activity paradigms. Others suggest a periadolescent hypersensitivity to psychomotor stimulants such as nicotine in self-administration paradigms. Still others report no age differences in drug-induced motor activation or reward-related behavior. We have brought the question into our laboratory by testing acquisition and maintenance of intravenous amphetamine self-administration in periadolescent and adult, male and female rats.
- The Medial Prefrontal Cortex in Drug-Seeking Behavior during Adolescence: In adults, dopamine projections to the medial prefrontal cortex modulate cocaine self-administration and other drug-related behaviors. Given that this region is among the last areas of the brain to mature, it is likely to exert different effects on drug-seeking behavior in adolescent vs. adult subjects. We are interested in starting projects to test, a graduate student in the lab, is testing age differences in medial prefrontal cortical influence on cocaine self-administration by injecting dopaminergic compounds into that region prior to self-administration sessions. Chen has also conducted other studies on technical aspects of drug self-administration in periadolescent and adult rats.
- In Vivo Microdialysis: In order to examine the brain mechanisms involved in drug-related
behaviors, We are also interested in starting in neurochemical assays such as in vivo microdialysis and high performance liquid chromatography (HPLC). Of particular focus are interactions between dopamine and serotonin in the mesocorticolimbic pathways that underlie drug-induced behavioral stimulation and reinforcement.
A. Moffett, J. Johnson, and M. Shahbazi
