Details

Autor(en) / Beteiligte

• Tran-Nguyen, Ly Thi Luu

Titel

Time-dependent changes in cocaine-seeking behavior and dopamine overflow in the amygdala during cocaine withdrawal

Ort / Verlag

ProQuest Dissertations & Theses

Erscheinungsjahr

1997

Quelle

ProQuest Dissertations & Theses A&I

Beschreibungen/Notizen

• Cocaine and cocaine-paired cues elicit craving in humans and reinstate cocaine-seeking behavior (CSB) in rats. It has been suggested that craving and reinstatement of CSB may be mediated by time-dependent changes in dopamine (DA) neurotransmission that occur during the course of cocaine withdrawal. To examine this hypothesis, experimental rats were trained to press a lever for response-contingent intravenous (IV) cocaine administration and control rats received yoked IV saline administration. A light and tone were presented with the IV infusions. After 14 daily 3-hr training sessions, animals were assigned to groups that were tested after either a 1-day (1D), 1-week (1W), or 1-month (1M) withdrawal period. On the test day, baseline DA overflow in the amygdala was assessed and compared to DA overflow during extinction, cue reinstatement, and cocaine reinstatement of CSB (i.e., lever pressing in the absence of cocaine reinforcement). The extinction phase began after the animals were transferred to the operant chambers. After 2 hr, the cue reinstatement phase began by presenting the light and tone paired previously with the infusions. Two hr later, the cocaine reinstatement phase began by administering a priming injection of cocaine (15 mg/kg). The results clearly demonstrate a time-dependent enhancement in CSB, basal DA overflow, and cocaine-induced DA overflow following longer withdrawal periods. The enhancement in CSB suggests that the incentive motivational effects of cocaine become sensitized during the course of withdrawal. In addition, the elevation in basal DA overflow suggests a persistent alteration in homeostatic regulation of tonic DA release in the amygdala, while the enhancement in cocaine-induced DA overflow suggests a persistent sensitization of phasic DA release. The role of DA neurotransmission in the amygdala in CSB remains equivocal since the pattern of changes in these variables did not correspond during the extinction phase, but did correspond during the cocaine reinstatement phase. Several interpretations for the difference in the pattern of changes across test phases are discussed.