Behavioural, biochemical and molecular changes induced by chronic crack-cocaine inhalation in mice: The role of dopaminergic and endocannabinoid systems in the prefrontal cortex

被引：25

作者：

Areal, Lorena B. ^{[1
,2
]}

Rodrigues, Livia C. M. ^{[1
,3
]}

Andrich, Filipe ^{[1
,2
]}

Moraes, Livia S. ^{[1
,2
]}

Cicilini, Maria A. ^{[1
]}

Mendonca, Josideia B. ^{[4
]}

Pelicao, Fabricio S. ^{[4
]}

Nakamura-Palacios, Ester M. ^{[1
,3
]}

Martins-Silva, Cristina ^{[1
,2
]}

Pires, Rita G. W. ^{[1
,2
]}

机构：

[1] Univ Fed Espirito Santo, Hlth Sci Ctr, Dept Physiol Sci, Vitoria 29043910, Brazil

[2] Univ Fed Espirito Santo, Hlth Sci Ctr, Lab Mol & Behav Neurobiol, Vitoria 29043910, Brazil

[3] Univ Fed Espirito Santo, Hlth Sci Ctr, Lab Cognit Sci & Neuropsychopharmacol, Vitoria, Brazil

[4] Espirito Santo State Police, Lab Forens Sci Serv, BR-2290 Vitoria, Brazil

来源：

BEHAVIOURAL BRAIN RESEARCH | 2015年 / 290卷

关键词：

Crack-cocaine; Drug addiction; Dopaminergic system; Endocannabinoid system; Prefrontal cortex; ANHYDROECGONINE METHYL-ESTER; DRUG-ADDICTION; D2; RECEPTORS; GENE-EXPRESSION; DELTA-FOSB; REWARD; METHYLECGONIDINE; HYDROCHLORIDE; DYSREGULATION; SENSITIZATION;

D O I：

10.1016/j.bbr.2015.04.036

中图分类号：

B84 [心理学]; C [社会科学总论]; Q98 [人类学];

学科分类号：

03 ; 0303 ; 030303 ; 04 ; 0402 ;

摘要：

Crack-cocaine addiction has increasingly become a public health problem worldwide, especially in developing countries. However, no studies have focused on neurobiological mechanisms underlying the severe addiction produced by this drug, which seems to differ from powder cocaine in many aspects. This study investigated behavioural, biochemical and molecular changes in mice inhaling crack-cocaine, focusing on dopaminergic and endocannabinoid systems in the prefrontal cortex. Mice were submitted to two inhalation sessions of crack-cocaine a day (crack-cocaine group) during 11 days, meanwhile the control group had no access to the drug. We found that the crack-cocaine group exhibited hyperlocomotion and a peculiar jumping behaviour ("escape jumping"). Blood collected right after the last inhalation session revealed that the anhydroecgonine methyl ester (AEME), a specific metabolite of cocaine pyrolysis, was much more concentrated than cocaine itself in the crack-cocaine group. Most genes related to the endocannabinoid system, CBI receptor and cannabinoid degradation enzymes were downregulated after 11-day crack-cocaine exposition. These changes may have decreased dopamine and its metabolites levels, which in turn may be related with the extreme upregulation of dopamine receptors and tyrosine hydroxylase observed in the prefrontal cortex of these animals. Our data suggest that after 11 days of crack-cocaine exposure, neuroadaptive changes towards downregulation of reinforcing mechanisms may have taken place as a result of neurochemical changes observed on dopaminergic and endocannabinoid systems. Successive changes like these have never been described in cocaine hydrochloride models before, probably because AEME is only produced by cocaine pyrolysis and this metabolite may underlie the more aggressive pattern of addiction induced by crack-cocaine. (C) 2015 Elsevier B.V. All rights reserved.

引用

页码：8 / 16

页数：9

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