Morphine-induced conditioned place preference in rhesus monkeys: Resistance to inactivation of insula and extinction.
Drug addicts experience strong craving episodes in response to drug-associated cues. Attenuating these responses using pharmacological or behavioral approaches could aid recovery from addiction. Cue-induced drug seeking can be modeled using the conditioned place preference procedure (CPP). Our previous work showed that conditioned place preference (CPP) can be induced by administration of increasing doses of morphine in rhesus monkeys. Here, we investigated whether expression of morphine-induced CPP can be attenuated by inhibiting activity of insular cortex or by repeated unreinforced exposures to the CPP test. The insula has been demonstrated to be involved in addiction to several drugs of abuse. To test its role in morphine CPP, bilateral cannulae were implanted into the insula in seven adult monkeys. The CPP was established using a biased apparatus by intramuscular injections of morphine at increasing doses (1.5, 3.0 and 4.5mg/kg) for each monkey. After the monkeys established morphine CPP, their insulae were reversibly inactivated by bilateral microinjection with 5% lidocaine (40μl) prior to the post-conditioning test (expression) of CPP using a within-subject design. The microinjections of lidocaine failed to affect CPP expression when compared to saline injections. We subsequently investigated morphine-associated memory during six episodes of CPP tests performed in these monkeys over the following 75.0±0.2months. While the preference score showed a declining trend with repeated testing, morphine-induced CPP was maintained even on the last test performed at 75months post-conditioning. This observation indicated strong resistance of morphine-induced memories to extinction in rhesus monkeys. Although these data do not confirm involvement of insula in morphine-induced CPP, our observation that drug-associated memories can be maintained over six drug-free years following initial experience with morphine has important implications for treatment of drug addiction using extinction therapy.
Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China; Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, China.
XuJun
X
Wu
Second Department of Neurosurgery, First Affiliated Hospital of Kunming Medical University, Kunming, China.
Ning
N
Zhao
Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China.
Fan
F
Bai
Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China.
ChuanYu
C
Li
Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China.
CiRong
C
Liu
Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China; Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, China.
JingKuan
J
Wei
Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China.
Wei
W
Zong
State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China.
LiXin
L
Yang
Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR, USA.
Andrey E
AE
Ryabinin
Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China.
YuanYe
Y
Ma
Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China. Electronic address: wangjh@mail.kiz.ac.cn.
JianHong
J
Wang
D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects*; D003214:Conditioning, Classical / Q000187:drug effects*; D005108:Extinction, Psychological / Q000502:physiology*; D008012:Lidocaine / Q000008:administration & dosage / Q000494:pharmacology; D008253:Macaca mulatta; D008568:Memory / Q000502:physiology*; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D009294:Narcotics / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors; D061567:Voltage-Gated Sodium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology
D009294:Narcotics; D061567:Voltage-Gated Sodium Channel Blockers; D009020:Morphine; D008012:Lidocaine
Conditioned place preference (CPP); Extinction; Insula; Morphine associated memory; Rhesus monkey