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

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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.

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