RESUMEN
Transcription factor DeltaFosB has been implicated in the psychomotor responses and rewarding effects of drugs of abuse. In the present study, we compared the effects of cocaine on the expression of DeltaFosB-like proteins by immunohistochemistry in striatal brain areas of alcohol-preferring (AA) and alcohol-avoiding (ANA) rats. Cocaine was administered using a previously verified treatment paradigm that sensitized the locomotor response to cocaine in AA but not in ANA rats. We also studied the rewarding effects of cocaine with a conditioned place preference (CPP) paradigm in both lines of rats. Cocaine treatment increased the FosB/DeltaFosB immunoreactivity (IR) in the nucleus accumbens of AA rats but not in ANA rats. In addition, after repeated saline injections the accumbal FosB/DeltaFosB IR was significantly greater in saline-injected AA rats than in ANA rats. In the caudate-putamen cocaine significantly increased FosB/DeltaFosB IR, but no differences were found between the rats of two lines. In the CPP experiment, AA rats treated with cocaine 2.5 mg/kg preferred the cocaine-associated compartment, in contrast to ANA rats, which did not show such a preference. In conclusion, our findings show that AA rats are more sensitive to cocaine than ANA rats, and suggest that one possible mediator for this increased sensitivity could be the increased expression of fosB-derived proteins in the nucleus accumbens of AA rats.
Asunto(s)
Consumo de Bebidas Alcohólicas/metabolismo , Anestésicos Locales/administración & dosificación , Cocaína/administración & dosificación , Condicionamiento Operante/efectos de los fármacos , Núcleo Accumbens/efectos de los fármacos , Proteínas Proto-Oncogénicas c-fos/metabolismo , Consumo de Bebidas Alcohólicas/genética , Análisis de Varianza , Animales , Conducta Animal , Esquema de Medicación , Regulación de la Expresión Génica/efectos de los fármacos , Masculino , Núcleo Accumbens/metabolismo , Ratas , Factores de TiempoRESUMEN
DeltaFosB, a member of Fos family of transcription factors, is implicated in behavioural responses and synaptic plasticity induced by abused drugs. We studied the expressions of FosB/DeltaFosB and c-Fos immunohistochemically in two dopaminergic brain areas, nucleus accumbens (NAcc) and caudate-putamen (CPu). In mice neither 2- nor 7-week oral nicotine treatment induced expression of long-lived DeltaFosB isoforms although during the treatment in the NAcc FosB/DeltaFosB expression was increased as was c-Fos in the CPu. In rats given nicotine subcutaneously once daily for 5days FosB/DeltaFosB expression was elevated in the NAcc still after 24-h withdrawal suggesting accumulation of DeltaFosB but in the CPu neither FosB/DeltaFosB nor c-Fos expression was altered. Thus, in rats repeated nicotine administration seems mainly affect the NAcc paralleling with the evidence that nicotine stimulates preferentially mesolimbic dopamine system. Also, repeated nicotine induced behavioural sensitization in rats agreeing with suggested role of DeltaFosB in the development of psychomotor sensitization. However, in mice given nicotine via drinking fluid although striatal fosB and c-fos were activated by nicotine even after 7-week treatment no evidence of accumulation of long-lived DeltaFosB was found suggesting perhaps a species difference or more likely a role for the manner of administration.