[Animal models of drug dependence using the drug self-administration method].
This paper will review 1) experimental models of drug-seeking behavior and 2) mechanisms underlying the behavior, focusing on cocaine self-administration. After the acquisition of self-administration, vigorous lever-pressing is generally observable after the drug was replaced by saline. This lever-pressing behavior under saline infusion can be considered "drug-seeking behavior". Drug-seeking behavior is reinstated by non-contingent injection of the drug, stress exposure and presentation of drug-associated stimuli even after extinction. This is called a relapse/reinstatement model. Electrophysiological studies showed that the majority of accumbal neurons is tonically inhibited during cocaine self-administration and exhibited phasic increases in firing time-locked to cocaine self-infusion, which might represent the craving state or drive animals to drug-seeking behavior. Voltammetry and microdialysis studies indicated that the timing of drug-seeking responses can be predicted from fluctuations in accumbal extracellular dopamine concentration. Whereas dopamine D2-like agonists reinstated extinguished cocaine-seeking behavior, D1-like agonists prevented the relapse in cocaine-seeking behavior induced by cocaine itself. Given that an AMPA receptor antagonist, but not dopamine antagonist, prevented cocaine-seeking behavior induced by cocaine, glutamate transmission in the nucleus accumbens is thought to be important for expression of craving or drug-seeking behavior.
Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashiku, Fukuoka 812-8582, Japan. tyamamot@phar.kyushu-u.ac.jp
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Yamamoto
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Yabuuchi
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Yamaguchi
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Nakamichi
D000818:Animals; D000242:Cyclic AMP / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D004195:Disease Models, Animal; D004298:Dopamine / Q000502:physiology; D018698:Glutamic Acid / Q000502:physiology; D006801:Humans; D009474:Neurons / Q000502:physiology; D009714:Nucleus Accumbens / Q000502:physiology; D012008:Recurrence; D012054:Reinforcement, Psychology; D012646:Self Administration; D013312:Stress, Physiological; D019966:Substance-Related Disorders / Q000523:psychology
D018698:Glutamic Acid; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D004298:Dopamine