Unterwald E M, Cox B M, Kreek M J, Cote T E, Izenwasser S
Rockefeller University, New York, New York 10021.
Synapse. 1993 Sep;15(1):33-8. doi: 10.1002/syn.890150104.
Repeated daily cocaine injections have been shown to alter mu-opioid receptor densities in the caudate putamen and nucleus accumbens of rat brain (Unterwald et al., 1991, 1992). Adenylyl cyclase activity was measured in rat rostral caudate putamen and nucleus accumbens following repeated cocaine administration to determine the functional consequences of cocaine-induced opioid receptor changes. Male Fischer rats were injected daily for 14 days with saline or cocaine HCl (30 or 45 mg/kg/day, i.p.) in three equal doses at 1-hr intervals. Basal adenylyl cyclase activity and the effects of the selective mu- and delta-opioid agonists [D-Ala2,N-Me-Phe4,Gly-ol5]enkephalin (DAMGO) and [D-penicillamine2,D-Penicillamine5]enkephalin (DPDPE), respectively, on adenylyl cyclase activity were examined 30 min after the last injection using a cAMP radioligand binding assay in crude membrane preparations. Basal adenylyl cyclase activity was 49% and 34% lower in the caudate putamen of animals treated with 30 and 45 mg/kg/day of cocaine, respectively, as compared to those receiving saline injections. Basal adenylyl cyclase activity was unchanged in the nucleus accumbens following cocaine treatment. DAMGO and DPDPE each maximally inhibited approximately 25% and 30%, respectively, of basal adenylyl cyclase in the caudate putamen and nucleus accumbens of saline-injected animals. Administration of cocaine attenuated the ability of DPDPE to inhibit adenylyl cyclase in both brain regions, but had no effect on the efficacy or potency of DAMGO for inhibiting adenylyl cyclase activity. These results suggest that chronic, repeated cocaine administration results in a selective impairment of delta-opioid receptor-mediated effector function in the caudate putamen and nucleus accumbens.
每日重复注射可卡因已被证明会改变大鼠脑尾状壳核和伏隔核中的μ-阿片受体密度（Unterwald等人，1991年，1992年）。在对大鼠反复给予可卡因后，测量其吻侧尾状壳核和伏隔核中的腺苷酸环化酶活性，以确定可卡因诱导的阿片受体变化的功能后果。雄性Fischer大鼠每天注射14天，分别注射生理盐水或盐酸可卡因（30或45mg/kg/天，腹腔注射），分三个等份剂量，间隔1小时。在最后一次注射后30分钟，使用粗膜制剂中的cAMP放射性配体结合测定法，检测基础腺苷酸环化酶活性以及选择性μ-和δ-阿片受体激动剂[D-Ala2，N-Me-Phe4，Gly-ol5]脑啡肽（DAMGO）和[D-青霉胺2，D-青霉胺5]脑啡肽（DPDPE）对腺苷酸环化酶活性的影响。与接受生理盐水注射的动物相比，分别用30和45mg/kg/天可卡因处理的动物的尾状壳核中基础腺苷酸环化酶活性分别降低了49%和34%。可卡因处理后，伏隔核中的基础腺苷酸环化酶活性没有变化。在注射生理盐水的动物的尾状壳核和伏隔核中，DAMGO和DPDPE分别最大程度地抑制了基础腺苷酸环化酶的约25%和30%。给予可卡因减弱了DPDPE在两个脑区抑制腺苷酸环化酶的能力，但对DAMGO抑制腺苷酸环化酶活性的效力或效能没有影响。这些结果表明，长期、反复给予可卡因会导致尾状壳核和伏隔核中δ-阿片受体介导的效应器功能选择性受损。
