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The Journal of Neuroscience, May 31, 2006, 26(22):6004-6010; doi:10.1523/JNEUROSCI.4494-05.2006

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Behavioral/Systems/Cognitive
Activation of Muscarinic and Nicotinic Acetylcholine Receptors in the Nucleus Accumbens Core Is Necessary for the Acquisition of Drug Reinforcement

Jose A. Crespo, Katja Sturm, Alois Saria, and Gerald Zernig

Division of Neurochemistry, Department of Psychiatry, Medical University Innsbruck, A-6020 Innsbruck, Austria

Correspondence should be addressed to Dr. Gerald Zernig, Division of Neurochemistry, Department of Psychiatry, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck, Austria. Email: gerald.zernig{at}uibk.ac.at

Neurotransmitter release in the nucleus accumbens core (NACore) during the acquisition of remifentanil or cocaine reinforcement was determined in an operant runway procedure by simultaneous tandem mass spectrometric analysis of dopamine, acetylcholine, and remifentanil or cocaine itself. Run times for remifentanil or cocaine continually decreased over the five consecutive runs of the experiment. Intra-NACore dopamine, acetylcholine, and drug peaked with each intravenous remifentanil or cocaine self-administration and decreased to pre-run baseline with half-lives of 10 min. As expected, remifentanil or cocaine peaks did not vary between the five runs. Surprisingly, however, drug-contingent dopamine peaks also did not change over the five runs, whereas acetylcholine peaks did. Thus, the acquisition of drug reinforcement was paralleled by a continuous increase in acetylcholine overflow in the NACore, whereas the overflow of dopamine, the expected prime neurotransmitter candidate for conditioning in drug reinforcement, did not increase. Local intra-accumbens administration by reverse microdialysis of either atropine or mecamylamine completely and reversibly blocked the acquisition of remifentanil reinforcement. Our findings suggest that activation of muscarinic and nicotinic acetylcholine receptors in the NACore by acetylcholine volume transmission is necessary during the acquisition phase of drug reinforcement conditioning.

Key words: remifentanil; cocaine; nucleus accumbens core; acetylcholine; dopamine; acquisition; reinforcement; runway; muscarinic; nicotinic

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Received June 23, 2005; revised April 16, 2006; accepted April 24, 2006.

Correspondence should be addressed to Dr. Gerald Zernig, Division of Neurochemistry, Department of Psychiatry, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck, Austria. Email: gerald.zernig{at}uibk.ac.at

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