Numerous studies suggest that people who prefer novel or arousing stimulation (e.g. high sensation- seekers) use drugs more frequently than low sensation seekers. Thus, high sensation-seekers may be predisposed biologically to find both novel stimuli and drugs to be more rewarding than low sensation- seekers. The long-term goal of this research is to determine if individuals who prefer novel and arousing stimuli share a common neuroanatomical mechanism using an animal model. Rats that are highly active in a novel environment (high responders) are more sensitive to amphetamine-induced locomotor activity and self-administer more amphetamine compared to rats that are relatively inactive (low responders). Previous research has demonstrated that inactivation of the central nucleus of the amygdala (ACe) reduces amphetamine self-administration only in high responder rats. The overall mechanistic framework for the proposed set of experiments is based on the role of the ACe in regulating arousal due to its extensive cortical and subcortical projections. The hypothesis is that the ACe is more active in high responder rats compared to low responder rats. The effects of inactivation of the ACe on subsequent amphetamine- induced locomotor activity will be measured to determine if the ACe contributes to the increased sensitivity of high responder rats to amphetamine-induced locomotor activity. Further, the amount of conditioned activity in an amphetamine-associated environment will be measured to determine if the ACe contributes to conditioned activity and if high responder and low responder rats differ in conditioned activity. In addition, the amount of c-fos expression will be measured in the ACe to determine if the ACe has greater activity in high responder rats. The findings of these experiments are intended to advance the understanding of vulnerability for stimulant abuse, and will potentially lead to better prevention and treatment interventions. ? ? ?
| Lucchesi, Valentina; Hurst, Dow P; Shore, Derek M et al. (2014) CB2-selective cannabinoid receptor ligands: synthesis, pharmacological evaluation, and molecular modeling investigation of 1,8-Naphthyridin-2(1H)-one-3-carboxamides. J Med Chem 57:8777-91 |
| Cain, Mary E; Mersmann, Marian G; Gill, Margaret J et al. (2012) Dose-dependent effects of differential rearing on amphetamine-induced hyperactivity. Behav Pharmacol 23:744-53 |
| Cain, Mary E; Coolon, Rosemary A; Gill, Margaret J (2009) The contribution of the central nucleus of the amygdala to individual differences in amphetamine-induced hyperactivity. Behav Brain Res 202:11-8 |
