The hypothesis that separate neural systems mediate the reinforcing properties of opioid and psychomotor stimulant drugs was tested by examining the role of mesolimbic dopamine (DA) neurons in maintaining intravenous heroin and cocaine self-administration. After local destruction of the DA terminals in the nucleus accumbens (NAcc) with 6-hydroxydopamine (6-OHDA), rats trained to self-administer cocaine and heroin on alternate days were observed for changes in their drug-seeking behaviors. Postlesion responding for cocaine showed a time-dependent decrease or extinction, whereas heroin self-administration showed a time-dependent recovery. By the fifth trial postlesion, heroin self-administration had recovered to 76% of prelesion baseline levels, but cocaine self-administration had dropped to 30% of prelesion baseline rates. Thus, selective lesions of the DA terminals in the nucleus accumbens significantly attenuate cocaine but not heroin self-administration. These data support the hypothesis that independent neural substrates are responsible for the reinforcing actions of these two drugs.

The hypothesis that separate neural systems mediate the reinforcing properties of opiate and psychomotor stimulant drugs was tested in rats trained to lever-press of IV injections of either cocaine or heroin during daily 3-h sessions. Pretreatment with the opiate receptor antagonist drug naltrexone produced dose-dependent increases in heroin self-administration, but had no effect on the rate or pattern of cocaine self-administration. Similarly, pretreatment with low doses of the dopamine antagonist drug alpha-flupenthixol produced dose-dependent increases in cocaine but not heroin self-administration. High doses of alpha-flupenthixol eliminated all responding for cocaine and slightly reduced heroin self-administration. The specificity with which the two antagonist drugs exerted their behavioral effects strongly suggests that independent neural substrates are responsible for the reinforcing actions of heroin and cocaine.

No abstract

Male albino rats were trained to traverse a straight alley for a reward of five intravenous injections of cocaine (0.75 mg/kg/injection in a volume of 0.1 ml/injection delivered over 4 s). Animals were tested one trial per day with the following dependent measures assessed on each trial: start latency, running time, the number of retreats, and the location within the alley where each retreat occurred. While start latencies remained short and stable, running times tended to increase over days. This effect was apparently related to a concomitant increase in the number of retreats occurring in the alley (r = 0.896). Retreats tended to occur in very close proximity to the goal box, suggesting that animals working for IV cocaine come to exhibit a form of conflict behavior (i.e., retreats) putatively stemming from the drug's well documented rewarding and anxiogenic properties. Consistent with this hypothesis was the demonstration that diazepam (0.5, 1.0, 2.0 mg/kg IP) pretreatment dose-dependently reduced the incidence of retreat behaviors in the alley. In addition, the rewarding efficacy of the cocaine dosing parameters was subsequently confirmed in the runway subjects by conditioned place preference. The present paradigm, therefore, provides a useful method for investigating the anxiogenic effects of self-administered cocaine in laboratory animals.