title: Exposure to repeated immobilization stress inhibits cocaine-induced increase in dopamine extracellular levels in the rat ventral tegmental area.
abstract: A higher vulnerability to drug abuse has been observed in human studies of individuals exposed to chronic or persistent stress, as well as in animal models of drug abuse. Here, we explored the effect of repeated immobilization stress on cocaine-induced increase in dopamine extracellular levels in VTA and its regulation by corticotropin-releasing factor (CRF) and GABA systems. Cocaine (10mg/Kg i.p.) induced an increase of VTA DA extracellular levels in control rats. However, this effect was not observed in repeated stress rats. Considering the evidence relating stress with CRF, we decided to perfuse CRF and CP-154526 (selective antagonist of CRF1 receptor) in the VTA of control and repeated stress rats, respectively. We observed that perfusion of 20μM CRF inhibited the increase of VTA DA extracellular levels induced by cocaine in control rats. Interestingly, we observed that in the presence of 10μM CP-154526, cocaine induced a significant increase of VTA DA extracellular levels in repeated stress rats. Regarding the role of VTA GABA neurotransmission, cocaine administration induced a significant increase in VTA GABA extracellular levels only in repeated stress rats. Consistently, cocaine was able to increase VTA DA extracellular levels in repeated stress rats when 100μM bicuculline, an antagonist of GABAA receptor, was perfused intra VTA. Thus, both CRF and GABA systems are involved in the lack of response to cocaine in the VTA of repeated stress rats. It is tempting to suggest that the loss of response in VTA dopaminergic neurons to cocaine, after repeated stress, is due to an interaction between CRF and GABA systems.
authors: Laboratorio de Neuroquímica y Neurofarmacología, Centro de Neurobiología y Plasticidad Cerebral, Instituto de Fisiología, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso, Chile. Electronic address: ramon.sotomayor@uv.cl.
authors: Ramón
authors: R
authors: Sotomayor-Zárate
authors: Laboratory of Cellular and Molecular Biology of Addiction, Department of Cellular and Molecular Biology, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors: Jorge
authors: J
authors: Abarca
authors: Laboratory of Cellular and Molecular Biology of Addiction, Department of Cellular and Molecular Biology, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors: Katherine A
authors: KA
authors: Araya
authors: Laboratorio de Neuroquímica y Neurofarmacología, Centro de Neurobiología y Plasticidad Cerebral, Instituto de Fisiología, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso, Chile.
authors: Georgina M
authors: GM
authors: Renard
authors: Laboratory of Cellular and Molecular Biology of Addiction, Department of Cellular and Molecular Biology, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors: María E
authors: ME
authors: Andrés
authors: Laboratory of Cellular and Molecular Biology of Addiction, Department of Cellular and Molecular Biology, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, Chile. Electronic address: kgysling@bio.puc.cl.
authors: Katia
authors: K
authors: Gysling
mesh_terms: D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D003042:Cocaine / Q000008:administration & dosage / Q000633:toxicity*; D019970:Cocaine-Related Disorders / Q000378:metabolism; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D045604:Extracellular Fluid / Q000378:metabolism; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D006801:Humans; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012149:Restraint, Physical / Q000009:adverse effects; D013312:Stress, Physiological; D017557:Ventral Tegmental Area / Q000187:drug effects* / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D058787:GABA-A Receptor Antagonists; D005680:gamma-Aminobutyric Acid; D003346:Corticotropin-Releasing Hormone; D003042:Cocaine; D004298:Dopamine; D001640:Bicuculline
keywords: Cocaine; Dopamine; Stress; VTA