The delayed effects of DTG and MK-801 on latent inhibition in a conditioned taste-aversion paradigm

The delayed effects of phencyclidine (PCP) have been shown to disrupt laten t inhibition (LI) in a conditioned taste-aversion paradigm. In an attempt t o understand the mechanism of this disruption. the delayed effects of the: selective sigma receptor agonist 1,3-Di(2-tolyl)guanidine (DTG) and the sel ective NMDA receptor antagonist MK-801 on latent inhibition were assessed i n the same paradigm. Water-deprived male rats were allowed access to either water (non-preexposed; NPE) or 5% sucrose (preexposed; PE) for 30 min on 2 consecutive days. On the third day, animals were allowed access to sucrose and subsequently injected with lithium chloride. On the forth day, animals were allowed access to both sucrose and water. LI was assessed by comparin g the percent sucrose consumed in PE and NPE groups on the fourth day. DTG (1.0, 5.0, or 10.0 mg/kg), MK-801 (0.5, 1.0, or 2.0 mg/kg), or vehicle was administered IP 20 h before preexposure (days 1 and 2) and conditioning (da y 3). In vehicle-treated groups. PE animals consumed a significantly higher percent sucrose on the test day than NPE animals, indicating the presence of LI. DTG (10.0 mg/kg) and MK-801 (2.0 mg/kg) decreased the percent sucros e consumed by animals in the PE group to the level observed in the NPE grou p, indicating disrupted LI. However: this dose of MK-801 was found to produ ce a decrease in percent sucrose consumed in PE animals not treated with li thium chloride, indicating that the decrease observed in the LI paradigm co uld be due to MK-801-induced decrease in taste preference for sucrose rathe r than a disruption of LI. Lower doses of MK-801 that did not produce a dec rease in taste preference fbr sucrose did not significantly disrupt LI. Non e of the doses of DTG tested altered taste preference for sucrose. These da ta suggest a role for sigma receptors in the previously observed PCP-induce d disruption of LI. Published by Elsevier Science Inc.. 2000.