Elsevier

Neuroscience

Volume 138, Issue 1, 2006, Pages 235-243
Neuroscience

Neuropharmacology
Effects of environmental and pharmacological stressors on c-fos and corticotropin-releasing factor mRNA in rat brain: Relationship to the reinstatement of alcohol seeking

https://doi.org/10.1016/j.neuroscience.2005.10.062Get rights and content

Abstract

We have observed marked heterogeneity among different stressors in their ability to reinstate alcohol seeking in rats. Of the stressors we have tested, only the environmental stressor footshock and the pharmacological stressor yohimbine induce reinstatement. The reasons for such differences among stressors are not known. The purpose of the experiments presented here is to determine the neuroanatomical substrates that underlie these behavioral differences. To this end, we assessed whether stressors effective in inducing reinstatement of alcohol seeking activate a different set of neuronal pathways than do those that are ineffective, using the technique of in situ hybridization of the mRNAs for c-fos, a marker of neuronal activation, and corticotropin-releasing factor (CRF), a stress-related peptide we have shown to be critical to footshock-induced reinstatement of alcohol seeking. Exposure of rats to the environmental stressors footshock, restraint or social defeat, or the pharmacological stressors yohimbine or FG-7142 increased levels of the mRNAs for c-fos and CRF in the brain in a number of areas previously shown to be responsive to stressors. We found regionally specific effects of the stressors on c-fos and CRF mRNA in brain regions associated with the rewarding effects of alcohol and other abused drugs. The two stressors we have previously shown to be effective in inducing reinstatement of alcohol seeking, footshock and yohimbine, induced c-fos mRNA in the shell of the nucleus accumbens, and the basolateral and central amygdalar nuclei. These two stressors also induced CRF mRNA in the dorsal region of the bed nucleus of the stria terminalis. Taken together, these results provide evidence that activity in these regions may be involved in the reinstatement of alcohol seeking induced by these stressors. These results are also in keeping with the previously demonstrated role of CRF neurons in the dorsal bed nucleus of the stria terminalis in the reinstatement of alcohol seeking induced by stress.

Section snippets

Animals

Fifty-six male Wistar rats (Charles River, Montreal, Quebec, Canada) weighing 300–350g were maintained at 22°C (light phase 07:00 h–19:00 h) with free access to food and water. Experimental procedures were done in compliance with guidelines of the Canadian Council on Animal Care, as well as those of National Institutes of Health Publication 85-23 (1996), and were approved by the animal care committee of the Centre for Addiction and Mental Health. In these experiments, all efforts were made to

c-fos mRNA

The effects of administration of the environmental stressors footshock, restraint or social defeat on c-fos mRNA in discrete regions of the rat brain are shown in Table 1, panel A. ANOVA revealed a significant effect of Stressor type in the three frontal cortical regions measured (MFC, OFC and ACg), the NACs, the septal nuclei (MS and LS), dBNST and vBNST, BLA and CeA, dHIPP, VTA, DRN and MRN and LC (P’s<0.05). Post hoc analysis of these regions revealed that all three stressors increased c-fos

Discussion

The purpose of the present study was to determine the neural substrates underlying the effectiveness of stressors in inducing reinstatement of alcohol seeking, using the technique of in situ hybridization of c-fos and CRF mRNA. We report differential effects of stressors in several brain regions previously shown to be involved in the rewarding effects of drugs of abuse. The two stressors effective in inducing reinstatement of alcohol seeking, the environmental stressor footshock and the

Acknowledgments

This work was support in part by grants from the Integrative Neuroscience Initiative on Alcoholism (East) to D. Funk and NIAAA (AA13108) to A. D. Lê.

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