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In Vivo monitoring of dopamine in the nucleus accumbens during intravenous self-administration of D-Amphetamine by the rat

University of British Columbia

Current theory suggests that mesolimbic dopamine (DA) in the nucleus accumbens is involved in the self-administration of drugs such as cocaine and amphetamine. The present thesis was conducted to determine some of the behavioural and in vivo dopaminergic correlates of intravenous (i.v.) self-administration of amphetamine in the rat. Experiment one tested the hypothesis that rats will self-administer amphetamine to maintain an optimal extracellular level of DA in the brain that exceeds a critical threshold. In vivo measurements of DA oxidation currents (electrochemical studies) and DA dialysate concentrations (microdialysis study) were used to determine changes in extracellular DA concentrations in rats permitted to self-administer 12 infusions of d-amphetamine a day at a given dose. During all self-administration sessions, distinct ‘loading’ and ‘maintenance’ phases were seen. The loading phase was characterized by rapid responding at the start of the session which slowed during the maintenance phase to a constant level for the duration of the selfadministration session. DA extracellular concentrations in the nucleus accumbens increased at the start of the self-administration session and then levelled off around a stable mean for the duration of the session. An inverse dose-response relationship between rate of responding for amphetamine and the dose of drug administered (0.05, 0.10 or 0.20 mg/infusion) was seen. No dose-related changes in the maximal increase in DA oxidation currents or dialysate concentrations during self administration was evident. Experiment two tested the hypothesis that increased DA levels associated with the reinitiation of responding after an abstinence serve as a negative reinforcer by increasing DA levels that are theoretically depleted during an abstinence (Dackis and Gold, 1985). When permitted continuous access to 0.10 mg/infusion of amphetamine for 48 hours, response rates and in vivo DA oxidation currents were similar to those in experiment one and remained steady during the course of the entire self-administration session. After at least 24 hours, all rats abstained from self-administering amphetamine for a single period of time lasting at least two hours. During this time, a decrease in DA concentrations was seen. Reinitiation of responding for amphetamine did not occur when DA concentrations were at their lowest, but was correlated with an immediate increase in DA concentrations as measured by in vivo electrochemistry. In summary, the findings of experiment one and two suggest that rats titer self-administered i.v. amphetamine to maintain a steady optimal extracellular level of DA in the brain that exceeds a reinforcement threshold.

Thesis/Dissertation

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2009-02-20

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http://hdl.handle.net/2429/4887

Psychology

University of British Columbia

UBCV

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