Neuropharmacology of the Interoceptive Stimulus Properties of Nicotine

Preclinical drug discrimination techniques play a significant role in advancing our knowledge of the receptor mechanisms underlying the interoceptive effects of nicotine. Early reports confirmed that nicotinic acetylcholine receptors (nAChRs) are critical for transduction of the nicotine cue. In recent years, advances in molecular biology and the discovery of novel ligands with greater selectively for specific nAChR subtypes have furthered our understanding of these mechanisms. There is now evidence regarding the specific nAChR subtypes involved in nicotine discrimination; in addition, there is also evidence suggesting that other systems (i.e., adenosine, cannabinoid, dopamine, glutamate and serotonin) may play a modulatory role. The neuroanatomical structures mediating the nicotine cue have also begun to be elucidated. However, much remains to be learned about the predictive validity of the drug discrimination procedure, particularly with regard to the relation between interoceptive and reinforcing effects and individual differences in vulnerability to tobacco dependence. Recent data also suggests that the mechanisms involved in the conditional and discriminative stimulus properties of nicotine may be dissociable. Avenues for future research should include assessing the mechanisms of the subjective effects of nicotine withdrawal, factors contributing to individual differences in sensitivity to the nicotine cue, and the role of behavioral factors involved in drug cross-substitution

Effects of Environmental Conditions on c-fos Expression in Rat Nucleus Accumbens After Remifentanil

Previous studies have shown that adolescents raised in impoverished conditions are more likely to develop drug abuse in adulthood. In addition, both stress-inducing living conditions (impoverishment/isolation) and drugs of abuse may lead to an increase in the c-fos transcription factor in the reward circuit of the brain, particularly in the nucleus accumbens. The aim of the current study was to quantify the number of c-fos positive cells in the nucleus accumbens of enriched and isolated rats exposed to the opioid remifentanil. Thirty-two male Sprague-Dawley rats were raised in either enriched or isolated conditions for one month, after which they received 10 i.v. infusions of 3 μg/kg remifentanil or saline through the jugular vein. Eighty-five minutes after the last infusion, rats underwent perfusions. After immunohistochemistry was performed on tissue containing the nucleus accumbens, the average number of c-fos positive cells per slice was obtained using ImageJ. Using a 2x2 between subjects ANOVA, with drug and environment as factors, this research demonstrated a main effect of environment on c-fos expression in the nucleus accumbens, with isolated rats expressing more c-fos positive cells than enriched rats. However, there was no significant effect of drug treatment, suggesting that remifentanil did not increase total c-fos as expected. This study demonstrated the cellular consequences of being raised in different living conditions, as it showed that individuals raised under high levels of stress may be at risk of altered cell signaling and gene expression in the reward system of the brain

Modified Single Prolonged Stress Reduces Cocaine Self-Administration During Acquisition Regardless of Rearing Environment

Until recently, there were few rodent models available to study the interaction of post-traumatic stress disorder (PTSD) and drug taking. Like PTSD, single prolonged stress (SPS) produces hypothalamic-pituitary-adrenal (HPA) axis dysfunction and alters psychostimulant self-administration. Other stressors, such as isolation stress, also alter psychostimulant self-administration. However, it is currently unknown if isolation housing combined with SPS can alter the acquisition or maintenance of cocaine self-administration. The current study applied modified SPS (modSPS; two hours restraint immediately followed by cold swim stress) to rats raised in an isolation condition (Iso), enrichment condition (Enr), or standard condition (Std) to measure changes in cocaine self-administration and HPA markers. Regardless of rearing condition, rats exposed to modSPS had greater corticosterone (CORT) release and reduced cocaine self-administration during initial acquisition compared to non-stressed controls. In addition, during initial acquisition, rats that received both Iso rearing and modSPS showed a more rapid increase in cocaine self-administration across sessions compared to Enr and Std rats exposed to modSPS. Following initial acquisition, a dose response analysis showed that Iso rats were overall most sensitive to changes in cocaine unit dose; however, modSPS had no effect on the cocaine dose response curve. Further, there was no effect of either modSPS or differential rearing on expression of glucocorticoid receptor (GR) in hypothalamus, medial prefrontal cortex, amygdala, or nucleus accumbens. By using modSPS in combination with Iso housing, this study identified unique contributions of each stressor to acquisition of cocaine self-administration

Neurochemical and Behavioral Effects of Acute and Chronic Treatment with Apomorphine in Rats

An article written by Bruce A. Mattingly and published by in the 1991 issue of Neuropharmacology, pages 191-197

Neurochemical Correlates of Behavior Sensitization Following Repeated Apomorphine Treatment: Assessment of the Role of D1 Dopamine Receptor Stimulation

An article written by Bruce A. Mattingly and published in the Spring 1993 issue of Synapse

Repeated Quinpirole Treatment: Locomotor Activity, Dopamine Synthesis and Effects of Selective Dopamine Antagonists

A report submitted by Bruce A. Mattingly the Research and Creative Productions Committee on the repeated treatment with the non-selective dopamine agonist apomorphine results in behavioral sensitization and enhanced dopamine synthesis in dopamine projection fields

Repeated Quinpirole Treatment: Locomotor Activity, Dopamine Synthesis, and Effects of Selective Dopamine Antagonists

An article written by Bruce A. Mattingly and published in Synapse in 1995 on repeated treatment with the non-selective dopamine agonist apomorphine results in behavioral sensitization and enhanced dopamine synthesis in dopamine projection fields