Regulation of Sensorimotor Gating of the Startle Reflex by Serotonin 2A Receptors. Ontogeny and Strain Differences

Sensorimotor gating of the startle reflex can be assessed via measures of prepulse inhibition (PPI), which is the reduction in startle magnitude when the startling stimulus is preceded immediately by a weak prepulse. PPI is reduced in humans with specific neuropsychiatric disorders and in rats after treatment with certain classes of drugs, including serotonin (5-HT) agonists. Because of the relative loss of PPI in inherited, neurodevelopmental disorders such as schizophrenia, there is great interest in understanding the inherited and developmental features of the neurochemical regulation of PPI in animals. In the present study, PPI was disrupted significantly by the 5-HT2A agonist 2, 5-dimethoxy-4 iodopheny-lisopropylamine (DOI) in Sprague Dawley (SDH) and Wistar rat strains (WH). While it was demonstrated that the DOI effects in SDH rats reflected an unequivocal disruption of sensorimotor gating, in WH rats, reduced PPI was observed in the context of a trend for a DOI-induced reduction in startle magnitude. This effect of DOI in SDH rats was evident at the earliest date tested (17 days of age) in male pups, but was not statistically significant in female pups. Thus, the regulation of sensorimotor gating by 5-HT2A receptor stimulation in rats may exhibit subtle differences across strains, and within SDH rats, between sexes. Most importantly, the 5-HT2A regulation of sensorimotor gating in male SDH rats is a "phenotype" that is expressed very early in life, and is sustained through adulthood.