Elsevier

Brain Research

Volume 616, Issues 1–2, 9 July 1993, Pages 315-319
Brain Research

Alterations of corticotropin-releasing factor-like immunoreactivity in different brain regions after acute cocaine administration in rats

https://doi.org/10.1016/0006-8993(93)90224-BGet rights and content

Abstract

Corticotropin-releasing factor (CRF) may mediate some of the neuroendocrine and behavioral responses to cocaine. In this study, the distribution of CRF-like immunoreactivity (CRF-LI) was determined in the hypothalamus and in several extrahypothalamic brain regions after acute cocaine administration in handled rats. CRF-LI decreased dose-dependently with cocaine administration in the hypothalamus and in the basal-forebrain structures. A small dose of cocaine (7.5 mg/kg) decreased CRF-LI in the hippocampus and in the frontal cortex. A significant, selective, dose-dependent increase in CRF-LI was found in the amygdala after cocaine injection. None of the investigated doses of cocaine altered CRF-LI in the striatum. These results suggest that acute cocaine administration alters brain CRF systems to contribute behavioral and neuroendocrine responses to cocaine.

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    One clear mechanism by which chronic drug use can alter stress response is via actions on CRF signaling. Acute administration of cocaine, morphine, nicotine, cannabinoids and alcohol lead to increases in CRF release, mRNA, and/or immunoreactivity [60–65]. While transient increases are seen following acute drug administration, chronic drug administration leads to sustained increases in CRF release [66,67] and CRF immunoreactivity [68].

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    In fact, cocaine can even stimulate the release of CRF from rat hypothalamic organ culture systems in vitro (Calogero, Gallucci, Kling, Chrousos, & Gold, 1989). Acute cocaine administration has also been reported to decrease CRF-like immunoreactivity in the hypothalamus, hippocampus, and frontal cortex, while increasing it in the amygdala (Sarnyai et al., 1993), indicating that cocaine can also affect CRF activity in areas located outside the hypothalamus. Similarly, chronic exposure to cocaine decreases CRF receptor binding in brain regions primarily associated with the mesocorticolimbic dopaminergic system (Goeders, Bienvenu, & De Souza, 1990).

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Present address: Alcohol and Drug Abuse Research Center, Harvard Medical School-McLean Hospital, 115 Mill Street, Belmont, MA 02178, USA.

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