Effects of dopamine receptor antagonism and amphetamine-induced psychomotor sensitization on sign- and goal-tracking after extended training

Abstract

Rationale. The dopamine system is thought to be important in incentive salience attribution, where motivational value is assigned to a cue that predicts an appetitive reinforcer (sign-tracking), however, dopamine's role may change with extended training. Objectives. We tested the effects of selective dopamine D1-like and D2-like receptor antagonism on the expression of Pavlovian conditioned approach after extended Pavlovian conditioned approach (PCA) training. We also tested the hypothesis that locomotor sensitization would accelerate the phenotypic shift to sign-tracking. Methods. 24 male Long-Evans rats were subjected to 20 PCA sessions in which one lever (CS+, 10 s) predicted 0.2 mL sucrose delivery and the other lever (CS-) did not. SCH-23390 or eticlopride were administered prior to behavioral tests at doses of 0, 0.01, and 0.1 mg/kg (s.c.). In a subsequent experiment, rats were exposed to vehicle or 2 mg/kg amphetamine (i.p.) for 7 days (n = 12/group). After a 10-day incubation period, they were subjected to PCA training for 16 sessions. Results. The D1 antagonist SCH-23390 reduced locomotor activity and port entries during inter-trial intervals, but the D2 antagonist eticlopride selectively reduced CS+ port entries in goal-trackers , i.e. animals motivated towards the reinforcer. Locomotor sensitization had no effect on the acquisition of sign-tracking. Conclusions. A commonly used dose of SCH-23390 exhibited off-target locomotor effects and D2 receptors were not required for expression of sign-tracking after extended training. Amphetamine-induced locomotor sensitization did not enhance acquisition of sign-tracking behavior, suggesting that the sensitivity of the dopamine system does not drive acquisition of sign-tracking behavior.

Dissociable mesolimbic dopamine circuits control responding triggered by alcohol-predictive discrete cues and contexts

“…Thus, dopamine neurotransmission at D1-like and D2-like receptors was required for port-directed behaviour, while CS-triggered alcohol-seeking required D2-like, but not D1like receptors. A reduction in NonCS port-entries may have been due to locomotor deficits caused by blocking dopamine receptors; however, the same dose of eticlopride used here did not impact locomotor behaviour in an open field 49,50 . Further, port-entries elicited by a CS that was paired with alcohol were unaffected by 10 μg per kg eticlopride 51 .…”