Effects of D3-preferring agonists 7-OH-PIPAT and PD-128,907 on motor behaviors and place conditioning

Dose-dependent effects of 7-OH-PIPAT and PD-128,907 on motor behaviors and place conditioning were examined in rats. Four 2-day conditioning trials were conducted over 8 consecutive days. On one day of each trial, animals received an injection of either saline, one of six doses of 7-OH-PIPAT (0.01-10.0 mg/kg), or one of five doses of PD-128,907 (0.01-1.0 mg/kg), and were placed into a distinct compartment for 40 min. On the other day, animals received an injection of saline and were placed into a different compartment for 40 min. Locomotion, sniffing, and yawning were measured following the first and last drug injections. Place conditioning was assessed the day following the last conditioning trial. None of the doses of 7-OH-PIPAT or 0-0.3 mg/kg PD-128,907 produced place conditioning. However, 1 mg/kg PD-128,907 produced conditioned place preference (CPP). Across doses, both 7-OH-PIPAT and PD-128,907 produced a U-shaped change in sniffing and locomotion and an inverted U-shaped change in yawning. Across time, lower doses produced a decrease in sniffing and locomotion and an increase in yawning that were evident immediately, whereas higher doses produced a biphasic change in that there was an initial decrease followed by an increase in sniffing and locomotion. Behaviors produced by both low and high doses were sensitized following repeated administration. PD-128,907 produced CPP and was more potent than 7-OH-PIPAT in altering motor behaviors, possibly due to its greater selectivity for the D3 receptor.