Chronic cocaine administration sensitizes behavioral but not neuroendocrine responses.
Many behavioral responses to cocaine become progressively exaggerated with chronic treatment. Most studies have focused on cocaine-induced locomotor stimulation and changes in the dopamine projection systems which mediate these actions. However, it is not clear if a uniform 'sensitization' develops in all dopamine systems during chronic stimulant administration. To test this possibility the neuroendocrine actions of cocaine which are mediated, in part, by hypothalamic dopamine neurons were evaluated after chronic cocaine administration. Treatment of rats with cocaine (15 mg/kg, 2x/day) markedly enhanced the locomotor response to cocaine after 3 and 7 days of chronic administration. In contrast, neither the stimulation of adrenocorticotropic hormone (ACTH)/corticosterone (CS) secretion nor the slight inhibition of prolactin caused by acute cocaine administration changed, although a small elevation of basal corticosterone secretion was observed after 7 days. These findings suggest that the marked sensitization observed in other dopamine systems does not occur in the hypothalamic dopamine neurons thought to mediate the neuroendocrine responses to cocaine during chronic administration, despite recently described commonalities in uptake and autoreceptor functions in these dopamine cell populations. This contrast suggests a role for long loop feedback systems unique to telencephalic dopamine systems or region-specific neurochemical adaptations in cocaine sensitization.
Borowsky
B
B
Department of Pharmacology, Duke University Medical Center, Durham, NC 27710.
Kuhn
C M
CM
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003042:Cocaine / Q000494:pharmacology*; D003345:Corticosterone / Q000097:blood; D004298:Dopamine / Q000378:metabolism; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009490:Neurosecretory Systems / Q000187:drug effects*; D011388:Prolactin / Q000097:blood; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains
D000324:Adrenocorticotropic Hormone; D011388:Prolactin; D003042:Cocaine; D004298:Dopamine; D003345:Corticosterone