PHNO, a selective dopamine D₂ receptor agonist, does not reduce prepulse inhibition of the startle reflex in rats

Abstract.

Rationale: Dopamine agonists nonselective for dopamine receptor subtypes, such as apomorphine, reduce prepulse inhibition of the startle reflex. It has been suggested that either D₂ or D₃ dopamine receptors mediate this action of apomorphine. Objective: The present study investigated whether a selective D₂ agonist with relatively low affinity for D₃ receptors can reduce prepulse inhibition. Methods: Rats (n=48) were treated with vehicle or one of three doses (15, 30 or 60 µg/kg, s.c.) of the specific dopamine D₂ receptor agonist (+)-4-propyl-9-hydroxynaphthoxazine (PHNO) for 11 days. On days 1, 6 and 11 of treatment, the rats (n=12 in each group) were tested for their acoustic startle reflexes (105-dB, 40-ms white noise) and for prepulse inhibition (5-kHz tone, 5 dB above a 65 dB background white noise). Prepulses were presented with a range of stimulus onset asynchronies (SOAs; 5–160 ms) or lead times between the onset of the prepulse and the onset of the startle stimulus. In a second experiment, two groups of rats (n=10 in each group) were tested in a similar manner after vehicle or apomorphine (0.8 mg/kg, s.c.) to verify the sensitivity of the present procedure to agonist-induced reductions in prepulse inhibition. Results: At doses that increased motor activity, PHNO increased prepulse inhibition at SOAs less than 80 ms and had no effect on prepulse inhibition at SOAs of 80 ms or above. However, all doses decreased startle amplitudes on trials in which only the startle-eliciting stimulus was presented. Apomorphine reduced prepulse inhibition under the same conditions. Conclusions: These findings with PHNO are in contrast to the less-specific D₂ agonist, quinpirole, which has been reported to decrease prepulse inhibition. It is concluded that activation of D₂ dopamine receptors alone is not sufficient to attenuate prepulse inhibition of the startle reflex.