A role for corticotropin-releasing factor in the long-term expression of behavioral sensitization to cocaine.
Corticotropin-releasing factor (CRF) has been implicated in a number of the behavioral and biochemical effects of cocaine. We recently reported that central injections of CRF produce a potentiated locomotor response in animals that had been given repeated injections of cocaine up to 4 weeks earlier. We now report that with as few as 1 or 3 exposures to cocaine (total of 45 mg/kg, i.p., per day), and a drug-free period of 28 days, i.c.v. injections of CRF (0.5 microg) produce augmented locomotor responses, similar to those induced by cocaine (10 mg/kg, i.p.) itself. In addition, in animals pre-exposed to cocaine for 3 days, pre-treatment with the CRF receptor antagonist, D-Phe CRF(12-41) (1 microg, i.c.v.), blocks the expression of behavioral sensitization to a cocaine challenge after a 28-day drug-free period. These results demonstrate that short-term exposure to cocaine produces a form of long-term sensitization within systems upon which CRF acts and that activation of CRF receptors is importantly involved in the expression of behavioral sensitization to cocaine.
Erb
Suzanne
S
Centre for the Neurobiology of Stress, Departments of Life Science and Psychology, University of Toronto at Scarborough, Toronto, Ontario, Canada. erb@utsc.utoronto.ca
Brown
Zenya J
ZJ
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D003042:Cocaine / Q000494:pharmacology*; D003346:Corticotropin-Releasing Hormone / Q000502:physiology*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007276:Injections, Intraventricular; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D013997:Time Factors
D018765:Dopamine Uptake Inhibitors; D003346:Corticotropin-Releasing Hormone; D003042:Cocaine