CHRONIC CONTINUOUS OR INTERMITTENT INFUSION OF COCAINE DIFFERENTIALLYALTER THE CONCENTRATION OF NEUROTENSIN-LIKE IMMUNOREACTIVITY IN SPECIFIC RAT-BRAIN REGIONS

Neurotensin (NT) is an endogenous brain tridecapeptide that exhibits s elective anatomic and neurochemical interactions with rat brain dopami nergic systems. Because modulation of dopaminergic neurotransmission m ay underlie many of the behavioral properties of cocaine, the effects of both acute and chronic administration of cocaine on the concentrati on of NT-like immunoreactivity (NT-LI) in specific brain regions was d etermined. Adult male rats were treated with cocaine for 14 days at a dose of 40 mg/kg/day (0.118 mmoles/kg/day) administered as either 1 su bcutaneous injection per day, or infused continuously using subcutaneo usly implanted minipumps. Neurotensin-like immunoreactivity in specifi c brain regions was then measured 24 hours or 8 days following drug ad ministration. After 24 hours of withdrawal from daily subcutaneous inj ection, the concentration of NT-LI was significantly increased in the substantia nigra (SN) and frontal cortex. After 24 hours of withdrawal from continuous infusion with cocaine, NT-LI was increased only in th e SN. After 8 days of withdrawal, NT-LI was increased in the SN of rat s treated with daily subcutaneous injections of cocaine, but not in th e group treated with continuous infusion. Twenty-four hours following a single acute injection of 40 mg/kg of cocaine, NT-LI was increased i n the SN and nucleus accumbens. These results provide evidence consist ent with a neuroanatomically selective involvement of NT systems in th e behavioral and/or addictive properties of cocaine.