Carey A N, Borozny K, Aldrich J V, McLaughlin J P
Department of Psychology, Northeastern University, Boston, MA 02115, USA.
Eur J Pharmacol. 2007 Aug 13;569(1-2):84-9. doi: 10.1016/j.ejphar.2007.05.007. Epub 2007 May 13.
Stress contributes to the reinstatement of cocaine-seeking behavior in abstinent subjects. Kappa-opioid receptor antagonists attenuate the behavioral effects of stress, potentially providing therapeutic value in treating cocaine abuse. Presently, the peptide arodyn produced long-lasting kappa-opioid receptor antagonism, suppressing kappa-opioid receptor agonist-induced antinociception at least 3 days after intracerebroventricular administration of 0.3 nmol. C57Bl/6J mice demonstrated cocaine-conditioned place preference, extinction over 3 weeks, and a subsequent reinstatement of place preference. Arodyn pretreatment suppressed stress-induced, but not cocaine-exposed, reinstatement of cocaine place preference. These results verify that arodyn and other kappa-opioid receptor antagonists may be useful therapeutics for cocaine abuse.
应激会促使戒断的个体恢复觅求可卡因的行为。κ-阿片受体拮抗剂可减弱应激的行为效应，这可能为治疗可卡因滥用提供治疗价值。目前，肽类药物阿罗定可产生持久的κ-阿片受体拮抗作用，在脑室内注射0.3 nmol后至少3天内抑制κ-阿片受体激动剂诱导的抗伤害感受。C57Bl/6J小鼠表现出可卡因条件性位置偏爱，经过3周消退后，位置偏爱随后又恢复。阿罗定预处理可抑制应激诱导的可卡因位置偏爱恢复，但不能抑制可卡因暴露诱导的恢复。这些结果证实，阿罗定和其他κ-阿片受体拮抗剂可能是治疗可卡因滥用的有效药物。
