The importance of baseline in identifying 8-OH-DPAT-induced effects on prepulse inhibition in rats

Background and purpose: Prepulse inhibition ( PPI) of the acoustic startle response is a model of sensorimotor gating which is disrupted in schizophrenia and other mental illnesses. We and others have shown that treatment with the 5- hydroxytryptamine-1A ( 5-HT1A) receptor agonist, 8-OH-DPAT, disrupts PPI in rats. In the present study, we highlight the importance of baseline levels on the effect of 8-OH-DPAT on PPI. Experimental approach: Adult male and female Sprague- Dawley rats were gonadectomised. These rats were treated with saline, 0.02 and 0.5 mg kg(-1) of 8-OH-DPAT using a random- sequence, repeated- measures protocol. The rats were allocated into high and low baseline groups depending on their baseline PPI observed after saline treatment. Key results: Treatment with 0.5 mg kg(-1) of 8-OH-DPAT significantly disrupted PPI in both male and female rats. In male rats only, 0.02 mg kg(-1) 8-OH-DPAT caused a small, but significant, increase in PPI. When these male rats were allocated to either a high or low baseline PPI group, 0.5 mg kg(-1) 8-OH-DPAT disrupted PPI in the high baseline group only. In contrast, treatment with 0.02 mg kg(-1) 8-OH-DPAT increased PPI only in the low baseline PPI group. There were no changes in the effect of 8-OH-DPAT administration in female rats when they were divided into high and low baseline PPI groups. Conclusions and implications: The level of baseline PPI is an important variable that can influence the direction of drug effects induced by 8-OH-DPAT. The explanation for this phenomenon could be differential activation of pre- and postsynaptic 5-HT1A receptors.