Differences in extracellular dopamine concentrations in the nucleus accumbens during response-dependent and response-independent cocaine administration in the rat

Abstract

Studies indicate that nucleus accumbens (NAcc) dopamine neurotransmission is involved in the reinforcing and direct effects of cocaine. The present study was initiated to explore further the relationship of NAcc extracellular dopamine concentrations ([DA]e) and cocaine self-administration using a yoked littermate design. In the first experiment, one rat from each litter was trained to self-administer cocaine i.v. (SA: 0.33 mg/inf) under a fixed ratio 2 schedule, while a second rat received simultaneous infusions of cocaine yoked to the infusions of the SA (YC). NAcc [DA]e and cocaine concentrations ([COC]) were assessed during the test sessions using in vivo microdialysis combined with microbore HPLC procedures. [DA]e and [COC] were significantly elevated in the SA and YC groups during the self-administration session; however, [DA]e were greater in the SA group compared to the YC group in the first hour of the session, even though [COC] were not significantly different. On the following day, the rats previously allowed to self-administer cocaine were administered response-independent cocaine infusions yoked to the infusion pattern from the previous day. [DA]e were significantly elevated above baseline levels during the session but were significantly less than concentrations obtained when cocaine was self-administered by these subjects. [COC] during the sessions were not significantly different between the two days. Baseline [DA]e were not significantly different between the SA and YC groups or between Day 1 and Day 2. Furthermore, there was no significant difference in the in vitro probe recovery between one and two days following probe implantation. These results suggest that the context in which cocaine was administered significantly altered the neurochemical response to equivalent brain concentrations of cocaine. NAcc [DA]e was significantly increased when the delivery of cocaine infusions was contingent on the behavior of the rat, indicative of a role in the neural processes underlying cocaine reinforcement.

Effects of Estradiol on Cocaine Self-Administration and Cocaine Discrimination by Female Rhesus Monkeys

“…This relatively rapid time course is consistent with evidence that estradiol has non-genomic effects that may precede its traditional genomic steroid actions and influence behavior as well as neuroendocrine and reproductive function (Falkenstein et al, 2000;Moore and Evans, 1999;Vasudevan and Pfaff, 2007;Wong et al, 1996). Both estradiol and cocaine increase extracellular dopamine levels measured in microdialysis studies in rodents (Becker, 1999;Becker et al, 2001;Di Chiara, 1995;Hemby et al, 1997), and dopamine is generally thought to subserve the reinforcing effects of cocaine (Kuhar et al, 1991;Woolverton and Johnson, 1992). The extent to which cocaine-induced increases in estradiol levels may contribute to cocaine-related increases in extracellular dopamine in the nucleus accumbens and ventral striatum is unknown.…”

Reinforcing effects of methylenedioxy amphetamine congeners in rhesus monkeys: are intravenous self-administration experiments relevant to MDMA neurotoxicity?

“…Finally, there is evidence that the contingencies governing drug administration can even affect neurochemical measures. In this regard, Hemby et al (1997) demonstrated significantly higher extracellular dopamine concentrations in the nucleus accumbens, despite equivalent brain concentrations of drug, in rats self-administering cocaine, as compared to a yoked control group. Furthermore, Stefanski et al (1999) observed region-specific downregulations of D 1 and D 2 receptors in rat brain after a 5-week regimen of methamphetamine self-administration but not after equivalent response-independent drug exposure using a yoked control design.…”

Cytosolic proteomic alterations in the nucleus accumbens of cocaine overdose victims

“…[6][7][8] These data support numerous studies in animal models demonstrating the role of the NAc in the reinforcing effects of cocaine. [9][10][11][12][13][14] Although regional and neurotransmitter-centric hypotheses have provided a framework for studying the acute and chronic effects of cocaine intake on the brain, detailed mechanisms of intracellular neuroadaptations have only recently become known. Repeated cocaine use induces biochemical adaptations in reinforcement-relevant brain regions [15][16][17] and these adaptations appear to be relevant to the processes of sensitization, craving, withdrawal and relapse.…”