title: Genetic differences in the modulation of accumbal glutamate and γ-amino butyric acid levels after cocaine-induced reinstatement.
abstract: The Lewis (LEW) and Fischer 344 (F344) inbred rat strains are frequently used to study the role of genetic factors in vulnerability to drug addiction and relapse. Glutamate and γ-amino butyric acid (GABA) transmission are significantly altered after cocaine-induced reinstatement, although whether LEW and F344 rats differ in their accumbal glutamate and GABA responsiveness to cocaine-induced reinstatement remains unknown. To investigate this, we measured by in vivo microdialysis extracellular glutamate and GABA levels in the core division of the nucleus accumbens after extinction of cocaine self-administration and during cocaine-induced reinstatement (7.5mg/kg, i.p.) in these two strains of rats. No strain differences were evident in cocaine self-administration or extinction behavior, although cocaine priming did induce a higher rate of lever pressing in LEW compared with F344 rats. After extinction, F344 rats that self-administered cocaine had less GABA than the saline controls, while the glutamate levels remained constant in both strains. There was more accumbal glutamate after cocaine priming in LEW rats that self-administered cocaine, while GABA levels were unaffected. By contrast, GABA increased transiently in F344 rats that self-administered cocaine, while glutamate levels were unaltered. In F344 saline controls, cocaine priming provoked contrasting effects in glutamate and GABA levels, inducing a delayed increase in glutamate and a delayed decrease in GABA levels. These amino acids were unaffected by cocaine priming in LEW saline rats. Together, these results suggest that genetic differences in cocaine-induced reinstatement reflect different responses of the accumbal GABA and glutamate systems to cocaine priming.
authors: Departamento de Psicología Básica I, Facultad de Psicología, UNED, Spain. mmiguens@psi.uned.es
authors: Miguel
authors: M
authors: Miguéns
authors: Fanny
authors: F
authors: Botreau
authors: Oscar
authors: O
authors: Olías
authors: Nuria
authors: N
authors: Del Olmo
authors: Santiago M
authors: SM
authors: Coria
authors: Alejandro
authors: A
authors: Higuera-Matas
authors: Emilio
authors: E
authors: Ambrosio
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D003042:Cocaine / Q000008:administration & dosage* / Q000494:pharmacology; D019970:Cocaine-Related Disorders / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D058999:Drug-Seeking Behavior; D019075:Electrophoresis, Capillary; D005108:Extinction, Psychological; D020022:Genetic Predisposition to Disease; D018698:Glutamic Acid / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D017551:Microdialysis / Q000379:methods; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D012008:Recurrence; D012646:Self Administration; D012965:Sodium Chloride / Q000008:administration & dosage; D013045:Species Specificity; D005680:gamma-Aminobutyric Acid / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*
chemical_list: D018765:Dopamine Uptake Inhibitors; D018698:Glutamic Acid; D012965:Sodium Chloride; D005680:gamma-Aminobutyric Acid; D003042:Cocaine