Restraint-induced corticosterone secretion and hypothalamic CRH mRNA expression are augmented during acute withdrawal from chronic cocaine administration

Abstract

Stress responses during cocaine withdrawal likely contribute to drug relapse and may be intensified as a consequence of prior cocaine use. The present study examined changes in stressor-induced activation of the hypothalamic-pituitary-adrenal (HPA) axis during acute withdrawal from chronic cocaine administration. Adult male Sprague-Dawley rats received daily administration of cocaine (30 mg/kg, i.p.) or saline for 14 days. Twenty-four hours after the last injection, rats in each group were sacrificed under stress-free conditions or following 30 min of immobilization. Plasma corticosterone (CORT) was measured in trunk-blood using radioimmunoassay, corticotropin-releasing hormone (CRH) mRNA levels in the paraventricular nucleus (PVN) of the hypothalamus were measured using in situ hybridization and glucocorticoid receptor (GR) protein expression in the pituitary gland and dissected brain regions was measured using Western blot analysis. Basal CRH mRNA in the PVN was unaltered as a result of prior cocaine administration. However, a significant increase in CRH mRNA was observed 90 min following the termination of restraint in cocaine withdrawn, but not saline-treated, rats. Basal CORT was also unaffected by prior cocaine administration, but the CORT response measured immediately after restraint was significantly augmented in cocaine-withdrawn rats. Differences in GR protein expression in number of regions implicated in negative feedback regulation of HPA function, including the hypothalamus, were not observed. These findings indicate that the HPA response to stressors is intensified during early withdrawal from cocaine administration and may be independent of changes in GR-mediated negative feedback.

Effects of single or repeated amphetamine treatment and withdrawal on lung allergic inflammation in rats

“…A subtype of VMAT called VMTA2 was cloned in neuronal cell population, blood cells and in histaminocytes [16]. Indirectly acting sympathomimetic drugs such as AMPH are potent amine-releasing and corticosterone-releasing agents that, among many other effects, interact with VMATs in vivo [10,16,30,31]. On the contrary, reserpine treatment inhibits vesicular amine uptake by binding irreversible to VMAT2 [13,29] and thus antagonizes some AMPH effects such as those driven by VMATs [10,13,16].…”

Neural regulation of endocrine and autonomic stress responses

“…Chronic drug exposure generally induces a chronic stress-like state in which basal tone of the HPA axis and ANS and/or their responses to stress are facilitated 188–191192–196 . The effects of chronic exposure to natural rewards have been little investigated, with the exception of chronic intake of palatable foods: in no-choice paradigms (e.g.…”

Stress, Dysregulation of Drug Reward Pathways, and the Transition to Drug Dependence

“…However, no differences were found for quantitative measures of CRF mRNA in the amygdala in a direct comparison of shortaccess long-access low-dose and long-access high-dose animals. Also, corticosterone and hypothalamic CRF mRNA are increased during acute withdrawal from long-term cocaine administration (62). Similar decreases in HPA activity have been observed with repeated alcohol administration in a binge model (63)(64)(65).…”