The effects of in vivo cocaine on norepinephrine-stimulated phosphoinositide hydrolysis in rat brain.
We examined the effects of a cocaine challenge on behavioral stimulation and NE-stimulated [3H]inositol-1-phosphate (IP1) formation in rat cerebral cortex after single (high dose) or repeated (low dose) cocaine administration. As previously reported, single high dose (40 mg/kg, IP) and repeated low dose (10 mg/kg, 8 IP injections) administrations of cocaine resulted in behavioral sensitization to a challenge injection of cocaine (10 mg/kg). In saline-pretreated animals, the acute cocaine challenge significantly potentiated the NE-stimulated [3H]IP1 formation as compared with the saline challenge, while in cocaine-pretreated animals, NE-stimulated phosphoinositide (PI) turnover was not significantly altered. These results suggest that although some of the acute effects of cocaine may be mediated by enhanced alpha 1-adrenergic receptor-linked PI hydrolysis, behavioral sensitization does not involve the alpha 1-adrenergic receptor-linked PI signal transduction system.
Illinois State Psychiatric Institute, Chicago.
J I
JI
Javaid
S C
SC
Pandey
J M
JM
Davis
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism*; D003042:Cocaine / Q000633:toxicity*; D003213:Conditioning, Psychological / Q000187:drug effects; D019204:GTP-Binding Proteins / Q000378:metabolism; D006868:Hydrolysis; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology*; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D013239:Stereotyped Behavior / Q000187:drug effects
D010716:Phosphatidylinositols; D018340:Receptors, Adrenergic, alpha-1; D019204:GTP-Binding Proteins; D003042:Cocaine; D009638:Norepinephrine