Cocaine Is Self-Administered into the Shell but Not the Core of the Nucleus Accumbens of Wistar Rats

Abstract

The rewarding properties of cocaine have been postulated to be regulated, in part, by the mesolimbic dopamine system. However, the possibility that the rewarding properties of cocaine are mediated by direct activation of this system has yielded contradictory findings. The intracranial self-administration technique is used to identify specific brain regions involved in the initiation of response-contingent behaviors for the delivery of a reinforcer. The present study assessed whether adult Wistar rats would self-administer cocaine directly into the nucleus accumbens shell (AcbSh) and core (AcbC). For each subregion, subjects were placed in standard two-lever operant chambers and randomly assigned to one of five groups for each site that were given either artificial cerebrospinal fluid (aCSF), or 400, 800, 1200, or 1600 pmol of cocaine/100 nl to self-administer. The data indicate that rats with placements within the AcbSh readily self-administered 800 to 1600 pmol of cocaine/ 100 nl and responded significantly more on the active than inactive lever. These subjects also decreased responding on the active lever when aCSF was substituted for cocaine and reinstated responding on the active lever when cocaine was reintroduced. Coinfusion of the D 2 -like receptor antagonist sulpiride inhibited cocaine self-infusion in the AcbSh. In contrast to the AcbSh data, rats failed to self-administer any tested dose of cocaine into the AcbC or areas ventral to the AcbSh. These findings suggest that the AcbSh is a neuroanatomical substrate for the reinforcing effects of cocaine and that activation of D2-like receptors is involved.

Regional Heterogeneity for the Intracranial Self-Administration of Ethanol and Acetaldehyde within the Ventral Tegmental Area of Alcohol-Preferring (P) Rats: Involvement of Dopamine and Serotonin

“…Animals used in the present study had no previous experience in the operant chambers. This rapid learning is in agreement with several studies in which the self-infusion of EtOH (Gatto et al, 1994;Rodd-Henricks et al, 2000, opioids (Bozarth and Wise, 1981;Devine and Wise, 1994), and GABA A antagonists (Ikemoto et al, 1997b) into the VTA, or D 1 -D 2 agonists (Ikemoto et al, 1997a) or cocaine (Rodd-Henricks et al, 2002a) into the shell of the nucleus accumbens were examined. The mechanisms underlying this rapid learning process are unknown but may be related to activation of the mesolimbic DA system produced by direct self-infusion of these agents.…”

“…Shortening the surgical times and increasing the reproducibility of placements are important considerations when large numbers of animals are used, comparisons across groups are being conducted, and highly accurate placements are required. Most of our previous ICSA studies used female rats (Ikemoto et al, 1997a, b;Gatto et al, 1994;Rodd-Henricks et al, 2000, 2002a, b, 2003. Although not systematically studied, the estrous cycle did not appear to significantly alter self-administration behavior, as indicated by fairly stable responding across several sessions, when the same concentration of EtOH (RoddHenricks et al, 2003) or ACD (Rodd-Henricks et al, 2002b) was given.…”

Impairment of acquisition of intravenous cocaine self-administration by RNA-interference of dopamine D1-receptors in the nucleus accumbens shell

“…The NAc shell, rather than the core, is also the area from which robust SA can be consistently obtained after response-contingent intracerebral infusion (Ikemoto, 2003;Rodd-Henricks et al, 2002), which, in turn, explains previous negative results obtained by infusions that did not specifically target the shell (Goeders and Smith, 1983).…”

Anabolic–androgenic steroid dependence? Insights from animals and humans

“…Drugs of abuse act on the mesolimbic DA system to increase DA release (amphetamine, opiates), or reduce DA reuptake by nerve terminals in Acb (cocaine) [17]. Moreover, rats will self-administer many drugs directly into Acb or VTA [43,143], and selective DA lesions attenuate the rewarding properties of food, sex, and drugs [147].…”

“…Drugs of abuse act on the mesolimbic DA system to increase DA release (amphetamine, opiates), or reduce DA reuptake by nerve terminals in Acb (cocaine) [17]. Moreover, rats will self-administer many drugs directly into Acb or VTA [43,143], and selective DA lesions attenuate the rewarding properties of food, sex, and drugs [147].Although we did not observe an increase in Fos expression in Acb in response to icv testosterone, a variety of evidence suggests that the activity of the mesolimbic DA system is involved in androgen reinforcement. Male rats will form a place preference when testosterone [123], DHT, is injected directly into Acb.…”