A systemically administered neurotensin agonist blocks disruption of prepulse inhibition produced by a serotonin-2A agonist

Prepulse inhibition (PPI) of the startle reflex can be disrupted by drugs that act as agonists at the serotonin (5-HT) 2A receptor, such as DOI, and this effect is blocked by drugs that inhibit 5-HT2A transmission. We tested the effects of systemic administration of PD 149 163, a neurotensin agonst, on DOI-induced disruption of PPI in Sprague-Dawley rats. PD 149 163 completely and dose dependently blocked the PPI deficits produced by DOI. These findings suggest that, in addition to their established ability to inhibit dopamine transmission, neurotensin agonists may also inhibit 5-HT2A transmission, a pharmacological feature associated with atypical antipsychotic drugs.