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 effect s of nicotine. In four separate experiments using rats, an environment repe atedly paired with nicotine acquired the ability to elicit increases in act ivity 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 grou p (Experiment I). In Experiment 2, control groups eliminated accounts based on nonspecific effects of nicotine and inhibitory conditioning decreasing activity in the unpaired controls of Experiment I. 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 loc omotor conditioning without impairing activity in controls (Experiment 3). In Experiment 4, pretreatment on the test day with the dopamine D-1 recepto r antagonist SCH-23390 (0.03 mg/kg) blocked expression of nicotine-conditio ned locomotor activity; the D-2/D-3, receptor antagonist eticlopride did no t. Thus, the dopamine D-1 receptor subtype appears to play a role in contex t-elicited increases in activity conditioned by nicotine; GABA may also mod ulate the expression of this conditioned effect. (C) 2001 Elsevier Science Inc. All rights reserved.