Longoni R, Spina L, Mulas A, Carboni E, Garau L, Melchiorri P, Di Chiara G
Institute of Experimental Pharmacology and Toxicology, University of Cagliari, Italy.
J Neurosci. 1991 Jun;11(6):1565-76. doi: 10.1523/JNEUROSCI.11-06-01565.1991.
In order to investigate the relative role of central delta- and mu-opioid receptors in behavior, the effects of (D-Ala2)deltorphin II, a natural delta-opioid peptide, and PL017, a beta-casomorphin derivative specific for mu receptors, were compared after local intracerebral and intraventricular administration. Intracerebral infusion of the two peptides was done bilaterally in the limbic nucleus accumbens and in the ventral and dorsal caudate putamen of freely moving rats through chronic intracerebral cannulas. After intra-accumbens infusion, the two peptides elicited marked but opposite behavioral effects: while (D-Ala2)deltorphin II evoked dose-dependent motor stimulation characterized by locomotion, sniffing, and oral stereotypies, PL017 elicited motor inhibition with rigidity and catalepsy. These effects were site specific because they could not be evoked from the ventral or from the dorsal caudate. Low doses of naloxone (0.1 mg/kg, s.c.) blocked the effects of PL017 but not those of (D-Ala2)deltorphin II, which instead were reduced by high doses of naloxone (1.0 mg/kg) and by the putative delta-antagonist naltrindole; this drug failed to affect the catalepsy induced by PL017. Therefore, while (D-Ala2)deltorphin II effects were delta-mediated, PL017 effects were mu-mediated. Blockade of dopamine D1 receptors by SCH 23390 abolished (D-Ala2)deltorphin II effects, while blockade of dopamine D2 receptors by raclopride or by haloperidol was without effect. Local application by reverse dialysis of (D-Ala2)deltorphin II (5 microM) to the accumbens resulted in a naloxone-sensitive increase of extracellular dopamine concentrations; these effects could not be evoked from the caudate, nor by PL017 in the accumbens. Intracerebroventricular administration of (D-Ala2)deltorphin II or of PL017 elicited behavioral effects qualitatively similar to those obtained from the accumbens.
为了研究中枢δ-阿片受体和μ-阿片受体在行为中的相对作用，比较了天然δ-阿片肽（D-Ala2）强啡肽II和对μ受体具有特异性的β-酪蛋白衍生肽PL017在脑内局部和脑室内给药后的作用。通过慢性脑内插管，在自由活动大鼠的伏隔核边缘以及腹侧和背侧尾状壳核双侧进行两种肽的脑内输注。在伏隔核内输注后，两种肽引起明显但相反的行为效应：（D-Ala2）强啡肽II引起剂量依赖性的运动刺激，表现为运动、嗅探和口部刻板行为，而PL017引起伴有僵硬和僵住症的运动抑制。这些效应具有位点特异性，因为它们不能从腹侧或背侧尾状核诱发。低剂量的纳洛酮（0.1mg/kg，皮下注射）可阻断PL017的作用，但不影响（D-Ala2）强啡肽II的作用，相反，高剂量的纳洛酮（1.0mg/kg）和假定的δ-拮抗剂纳曲吲哚可减弱（D-Ala2）强啡肽II的作用；该药物未能影响PL017诱导的僵住症。因此，（D-Ala2）强啡肽II的作用是由δ-介导的，而PL017的作用是由μ-介导的。SCH 23390对多巴胺D1受体的阻断消除了（D-Ala2）强啡肽II的作用，而雷氯必利或氟哌啶醇对多巴胺D2受体的阻断则没有效果。通过反向透析将（D-Ala2）强啡肽II（5μM）局部应用于伏隔核导致细胞外多巴胺浓度的纳洛酮敏感性增加；这些效应不能从尾状核诱发，也不能由PL017在伏隔核诱发。脑室内注射（D-Ala2）强啡肽II或PL017引起的行为效应在质量上与从伏隔核获得的效应相似。
