Daily cocaine self-administration under long-access conditions augments restraint-induced increases in plasma corticosterone and impairs glucocorticoid receptor-mediated negative feedback in rats. Brain Res 2007 Sep 05;1167:101-11
Date
08/11/2007Pubmed ID
17689506Pubmed Central ID
PMC2121305DOI
10.1016/j.brainres.2007.05.080Scopus ID
2-s2.0-34548133391 (requires institutional sign-in at Scopus site) 49 CitationsAbstract
Cocaine addiction appears to be associated with a drug-induced dysregulation of stressor responsiveness that may contribute to further cocaine use. The present study examined alterations in stressor-induced activation of the hypothalamic-pituitary-adrenal (HPA) axis in rats provided daily access to cocaine for self-administration (SA) under long-access conditions (1.0 mg/kg/infusion; 6 hx14 days). Cocaine self-administering rats displayed reduced basal plasma corticosterone (CORT) levels but showed an augmented restraint-induced percent increase response from baseline compared to saline self-administering controls when measured 24 days after SA testing. This augmented CORT response may have been attributable to impaired glucocorticoid receptor (GR)-mediated feedback regulation of HPA function, since cocaine self-administering rats were also less susceptible to dexamethasone (0.01 mg/kg, i.p.) suppression of plasma CORT levels. GR protein expression measured using Western blot analysis was significantly reduced in the dorsomedial hypothalamus (including the paraventricular nucleus [PVN]) but not in the pituitary gland, ventromedial hypothalamus, dorsal hippocampus, ventral subiculum, medial prefrontal cortex or amygdala in cocaine self-administering rats. Surprisingly, basal corticotropin-releasing hormone (CRH) mRNA or post-restraint increases in CRH mRNA measured at a single (90 min) time-point in the PVN using in situ hybridization did not differ between groups. The findings suggest that cocaine use produces persistent changes in individual responsiveness to stressors that may contribute to the addiction process.
Author List
Mantsch JR, Cullinan WE, Tang LC, Baker DA, Katz ES, Hoks MA, Ziegler DRAuthors
William E. Cullinan PhD Adjunct Associate Professor in the Neurosurgery department at Medical College of WisconsinJohn Mantsch PhD Chair, Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsBrain
Chronic Disease
Cocaine
Cocaine-Related Disorders
Corticosterone
Corticotropin-Releasing Hormone
Dopamine Uptake Inhibitors
Drug Administration Schedule
Feedback, Physiological
Hypothalamo-Hypophyseal System
Hypothalamus
Male
Pituitary-Adrenal System
RNA, Messenger
Rats
Rats, Sprague-Dawley
Receptors, Glucocorticoid
Restraint, Physical
Self Administration
Stress, Psychological
Time
