期刊
PSYCHOPHARMACOLOGY
卷 186, 期 2, 页码 143-149出版社
SPRINGER
DOI: 10.1007/s00213-006-0372-9
关键词
mGluR2/3; metabotropic glutamate receptor; cocaine; reinstatement; food-seeking; nucleus accumbens core; LY379268
资金
- NIDA NIH HHS [F31 DA018486, DA-12513, DA-18486, DA-05369] Funding Source: Medline
Rationale: Group II metabotropic glutamate receptor (mGluR2/3) agonists are proposed to serve as potential treatment for addiction. Objectives: The present study examined the hypothesis that mGluR2/3 agonists exert inhibitory effects on cocaine-induced reinstatement of cocaine-seeking. Methods: Rats were trained to self-administer either cocaine or control reinforcer (food), then responding on the reinforcer-paired lever was extinguished. Reinstatement of responding was induced by a noncontingent presentation of the self-administered reinforcer (10 mg/kg cocaine, i.p. or 765 mg of food). In one experiment, rats were systemically pretreated with vehicle (Veh) or the mGluR2/3 agonist LY379268 (0.3, 1, or 3 mg/kg, i.p.) 30 min before the reinstatement test session. In a second experiment, Veh or LY379268 (0.05, 0.5, or 5 nmol/side) was microinjected into the nucleus accumbens core (NAc core) 5 min before the reinstatement test session. The effects of LY379268 on cocaine- and food-induced reinstatement on reward seeking were assessed. Results: Both systemic and intra-NAc core pretreatment with LY379268 inhibited both cocaine- and food-seeking behavior. However, the effect of LY379268 appeared somewhat more effective for cocaine-seeking than food-seeking. Conclusions: These results support a potential therapeutic role for mGluR2/3 agonists on relapse of cocaine-seeking. However, doses that inhibited cocaine-seeking were only threefold lower than those inhibiting food-seeking, indicating possible unacceptable nonspecific effects. In addition, the NAc core is one site of action where the mGluR2/3 agonists elicit effects on reward-seeking behavior.
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