title: Accumbal and pallidal dopamine, glutamate and GABA overflow during cocaine self-administration and its extinction in rats.
abstract: We investigated the changes in dopamine (DA), glutamate and γ-aminobutyric acid (GABA) during cocaine self-administration in rats implanted with guide cannulae into the nucleus accumbens and ventral pallidum. After stabilized cocaine self-administration, separate groups of rats underwent extinction (10 days) procedure in which cocaine infusion was replaced by saline injections. With using a 'yoked' procedure, the effects of cocaine or its withdrawal on the level of neurotransmitters were evaluated by dual-probe microdialysis. Repeated cocaine administration reduced basal glutamate levels in the nucleus accumbens and ventral pallidum, whereas it did not affect basal accumbal DA levels. Only rats that self-administered cocaine had increased basal GABA overflow in both examined brain structures. Active or passive cocaine administration elevated extracellular accumbal DA, however, the extent of cocaine-evoked DA level was significantly higher in rats that self-administered cocaine while both groups of animals showed also an attenuation of GABA level in the nucleus accumbens. On day 10 of extinction training, rats previously given cocaine revealed decreases in the basal accumbal concentration of glutamate while the basal GABA levels were significantly enhanced as compared with baseline of saline-yoked controls. Potassium depolarization delayed the reduction of the accumbal and pallidal extracellular glutamate levels in the active and passive cocaine groups. The present data indicate that changes in DA and GABA neurotransmission during maintenance phase mirror the motivational aspects of cocaine intake. Depending on acute (24 hours) or late (10 days) cocaine withdrawal, different neurotransmitter systems (i.e. glutamate or GABA) seem to be involved.
authors: Laboratory of Drug Addiction Pharmacology, Department of Pharmacology, Institute of Pharmacology Polish Academy of Sciences, Poland.
authors: Karolina
authors: K
authors: Wydra
authors: Krystyna
authors: K
authors: Golembiowska
authors: Magdalena
authors: M
authors: Zaniewska
authors: Katarzyna
authors: K
authors: Kamińska
authors: Luca
authors: L
authors: Ferraro
authors: Kjell
authors: K
authors: Fuxe
authors: Małgorzata
authors: M
authors: Filip
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001479:Basal Ganglia / Q000187:drug effects / Q000378:metabolism*; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D058999:Drug-Seeking Behavior / Q000187:drug effects; D005108:Extinction, Psychological / Q000187:drug effects; D045604:Extracellular Fluid / Q000378:metabolism; D005971:Glutamates / Q000378:metabolism*; D008297:Male; D017551:Microdialysis / Q000379:methods; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D011189:Potassium Chloride / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012054:Reinforcement, Psychology; D012646:Self Administration; D012965:Sodium Chloride / Q000008:administration & dosage; D013375:Substance Withdrawal Syndrome / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects*; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D018765:Dopamine Uptake Inhibitors; D005971:Glutamates; D012965:Sodium Chloride; D005680:gamma-Aminobutyric Acid; D011189:Potassium Chloride; D003042:Cocaine; D004298:Dopamine