Effects of Haloperidol on Cue-induced Autonomic and Behavioral Indices of Heroin Reward and Motivation

Rationale: Most theoretical conceptions of motivation presume an internal state of sympathetic nervous system activation that precedes and accompanies goal-seeking behavior.

Objectives: The present study investigates the animals' physiological and behavioral response to presentation of environmental cues predictive of availability (S+) or non-availability (S-) of heroin in the goal box of a straight-arm alley.

Methods: Animals were trained to discriminate between two olfactory cues, one predictive of the delivery of i.v. heroin (0.1 mg/kg) upon the rat's entry into the goal box of the runway (the S+) and another cue (the S-) predictive of i.v. saline upon goal-box entry. Once discriminative performance had stabilized, animals were challenged with each of four haloperidol treatments in a counterbalanced manner (0.0, 0.075, 0.15, 0.3 mg/kg i.p.). Run times and heart rates (measured via radiotelemetry) served as the dependent variables on every trial.

Results: Both behavioral and physiological measures of motivation responded differentially to S+ and S- cues. Haloperidol had no effect during or immediately following S- trials, nor prior to reinforcer delivery on S+ trials. However, the behavioral and physiological consequences of heroin delivery during dopamine receptor antagonism were reliable - animals ran more slowly and showed less activation (lower heart rates) on the first S+ trial following a heroin + haloperidol experience.

Conclusions: The current data demonstrate that physiological and behavioral indices of cue-induced motivation remained intact during haloperidol challenge, while the reinforcing consequences of heroin appear to have been attenuated by dopamine receptor antagonism.