Comparison of nafadotride, CNQX, and haloperidol on acquisition versus expression of amphetamine-conditioned place preference in rats.

Neurotransmission at dopamine (DA) and glutamate synapses has been implicated in conditioning place preference (CPP) in rats, but different receptor subtypes may be differentially involved in acquisition and expression. A balanced CPP was used to study the role of DA D2 and D3 and glutamatergic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptors in acquisition and expression of amphetamine (2.0 mg/kg) CPP. We tested the DA D3 receptor-preferring antagonist nafadotride, the AMPA/kainate glutamate-receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione disodium salt (CNQX), and the DA D2 receptor-preferring antagonist haloperidol. The results revealed that nafadotride (0.5 mg/kg) and CNQX (0.05 mg/kg) blocked the expression of amphetamine CPP at a dose that failed to block acquisition. In contrast, haloperidol (0.1 mg/kg) blocked the acquisition of CPP at a dose that failed to block expression. Cotreatment with subthreshold doses of nafadotride (0.1 mg/kg) and CNQX (0.01 mg/kg) before the test session failed to block the expression of CPP. The results suggest that AMPA/kainate and DA D3 receptors are more strongly involved in the expression of amphetamine CPP and D2 receptors are more strongly involved in the acquisition of amphetamine CPP.