Ragnauth A, Moroz M, Bodnar R J
Department of Psychology and Neuropsychology Doctoral Sub-Program, Queens College, City University of New York, 65-30 Kissena Blvd., Flushing, NY 11367, USA.
Brain Res. 2000 Sep 8;876(1-2):76-87. doi: 10.1016/s0006-8993(00)02631-7.
The nucleus accumbens, and particularly its shell region, is a critical site at which feeding responses can be elicited following direct administration of opiate drugs as well as micro-selective and delta-selective, but not kappa-selective opioid receptor subtype agonists. In contrast to observations of selective and receptor-specific opioid antagonist effects upon corresponding agonist-induced actions in analgesic studies, ventricular administration of opioid receptor subtype antagonists blocks feeding induced by multiple opioid receptor subtype agonists. The present study examined whether feeding responses elicited by either putative mu ([D-Ala(2), NMe-Phe(4), Gly-ol(5)]-enkephalin (DAMGO)), delta(1) ([D-Pen(2), D-Pen(5)]-enkephalin (DPDPE)) or delta(2) ([D-Ala(2), Glu(4)]-deltorphin (Deltorphin)) opioid receptor subtype agonists administered into the nucleus accumbens shell were altered by accumbens pretreatment with either selective mu (beta-funaltrexamine), mu(1) (naloxonazine), delta(1) ([D-Ala(2), Leu(5), Cys(6)]-enkephalin (DALCE)), delta(2) (naltrindole isothiocyanate) or kappa(1) (nor-binaltorphamine) opioid receptor subtype antagonists. Similar magnitudes and durations of feeding responses were elicited by bilateral accumbens administration of either DAMGO (2.5 microg), DPDPE (5 microg) or Deltorphin (5 microg). DAMGO-induced feeding in the nucleus accumbens shell was significantly reduced by accumbens pretreatment of mu, delta(1), delta(2) and kappa(1), but not mu(1) opioid receptor subtype antagonists. DPDPE-induced feeding in the accumbens was significantly reduced by accumbens pretreatment of mu, delta(1), delta(2) and kappa(1), but not mu(1) opioid receptor subtype antagonists. Deltorphin-induced feeding in the accumbens was largely unaffected by accumbens delta(2) antagonist pretreatment, and was significantly enhanced by accumbens mu or kappa(1) antagonist pretreatment. These data indicate different opioid pharmacological profiles for feeding induced by putative mu, delta(1) and delta(2) opioid agonists in the nucleus accumbens shell, as well as the participation of multiple opioid receptor subtypes in the elicitation and maintenance of feeding by these agonists in the nucleus accumbens shell.
伏隔核，尤其是其壳区，是一个关键部位，直接给予阿片类药物以及微选择性和δ选择性（而非κ选择性）阿片受体亚型激动剂后，可引发进食反应。与镇痛研究中观察到的选择性和受体特异性阿片类拮抗剂对相应激动剂诱导作用的影响相反，脑室注射阿片受体亚型拮抗剂可阻断多种阿片受体亚型激动剂诱导的进食。本研究考察了预先向伏隔核壳区注射选择性μ（β-芬太尼）、μ1（纳洛酮嗪）、δ1（[D-青霉胺（2），D-青霉胺（5）]-脑啡肽（DPDPE））、δ2（[D-丙氨酸（2），谷氨酸（4）]-强啡肽（强啡肽））或κ1（去甲二氢吗啡酮）阿片受体亚型拮抗剂后，向伏隔核壳区注射假定的μ（[D-丙氨酸（2），N-甲基苯丙氨酸（4），甘醇（5）]-脑啡肽（DAMGO））、δ1（[D-青霉胺（2），D-青霉胺（5）]-脑啡肽（DPDPE））或δ2（[D-丙氨酸（2），谷氨酸（4）]-强啡肽（强啡肽））阿片受体亚型激动剂所引发的进食反应是否会发生改变。双侧伏隔核注射DAMGO（2.5微克）、DPDPE（5微克）或强啡肽（5微克）所引发的进食反应的幅度和持续时间相似。伏隔核壳区DAMGO诱导的进食在预先注射μ、δ1、δ2和κ1阿片受体亚型拮抗剂后显著减少，但预先注射μ1阿片受体亚型拮抗剂则无此效果。伏隔核中DPDPE诱导的进食在预先注射μ、δ1、δ2和κ1阿片受体亚型拮抗剂后显著减少，但预先注射μ1阿片受体亚型拮抗剂则无此效果。伏隔核中强啡肽诱导的进食在预先注射δ2拮抗剂后基本不受影响，而在预先注射μ或κ1拮抗剂后则显著增强。这些数据表明，假定的μ、δ1和δ2阿片激动剂在伏隔核壳区诱导进食时具有不同的阿片药理学特征，以及多种阿片受体亚型参与了这些激动剂在伏隔核壳区引发和维持进食的过程。
