Nicotine-conditioned locomotor activity in rats: Dopaminergic and GABAergic influences on conditioned expression

Little is known about the processes that mediate acquisition and expression of conditioned associations between contextual cues and psychomotor effects of nicotine. In four separate experiments using rats, an environment repeatedly paired with nicotine acquired the ability to elicit increases in activity even in the absence of drug. This conditioned effect was sensitive to nicotine dose. Rats that had 0.6 or 1.2 mg/kg nicotine, but not 0.3 mg/kg, paired with the environment were more active than an unpaired control group (Experiment 1). In Experiment 2, control groups eliminated accounts based on nonspecific effects of nicotine and inhibitory conditioning decreasing activity in the unpaired controls of Experiment 1. Pretreatment on the test day with 100 mg/kg of gamma vinyl-GABA (GVG), a compound that inhibits the enzyme required to breakdown GABA, partially blocked the expression of locomotor conditioning without impairing activity in controls (Experiment 3). In Experiment 4, pretreatment on the test day with the dopamine D₁ receptor antagonist SCH-23390 (0.03 mg/kg) blocked expression of nicotine-conditioned locomotor activity; the D₂/D₃ receptor antagonist eticlopride did not. Thus, the dopamine D₁ receptor subtype appears to play a role in context-elicited increases in activity conditioned by nicotine; GABA may also modulate the expression of this conditioned effect.