Investigation into pharmacological factors predisposing rats to cocaine self-administration

Abstract

The present dissertation assessed the activating, reinforcing, and neurochemical responses to cocaine following amphetamine-, caffeine-, or nicotine-preexposure. Rats were given 9 daily injections of amphetamine (1.0 mg/kg, IP), caffeine (20.0 mg/kg, IP), nicotine (0.6 mg/kg, base weight, SC), or vehicle. On day 10 the animals were tested in one of three paradigms. Cocaine-induced activity was assessed in photo cell arenas. The reinforcement value of cocaine was estimated by the rate at which acquisition of cocaine self-administration occurred. The ability of cocaine to elevate synaptic levels of dopamine (DA) in the ventral striatum (VS) was quantified using the in vivo microdialysis technique. Preexposure to amphetamine or caffeine enhanced cocaine's activating effects. By contrast, nicotine-preexposure produced a suppression of cocaine-induced activity, an effect indicative of tolerance rather than sensitization. The reinforcing effects of cocaine were increased following preexposure to amphetamine, caffeine, or nicotine. These rats acquired cocaine self-administration at an enhanced rate relative to the vehicle-preexposed controls. Preexposure to amphetamine or caffeine augmented cocaine's ability to enhance synaptic levels of DA in the VS. Nicotine-preexposure produced a non-significant suppression of this effect. These data indicate that pharmacological treatments can differentially affect the activating and reinforcing effects of cocaine and are discussed in terms of relevance to the psychomotor stimulant theory of addiction.