Reduced brain serotonin activity disrupts prepulse inhibition of the acoustic startle reflex: Effects of 5,7-dihydroxytryptamine and p-chlorophenylalanine

These experiments examined the impact of extensive depletions of forebrain 53-hydroxytryptamine (5-HT; serotonin) levels on prepulse inhibition (PPI) of the acoustic startle reflex in rats. In Experiment 1 injection of the ne urotoxin 5,7-dihydroxytryptamine (5,7-DHT) into the dorsal and median raphe nuclei disrupted PPI. This deficit was observed beginning 2 clays after le sioning and was still apparent 8 weeks later. Basal startle reactivity was not altered. The 5-HT1A receptor agonist 8-OH-DPAT (0.1 mg/ kg) and the dop amine receptor agonist apomorphine (1mg/ kg) also disrupted PPI; the effect of 8-OH-DPAT, but not opomorphine, was potentaiated in 5-HT-depleted rats. Basal startle reactivity was enhanced by 8-OH-DPAT in sham-lesioned rats b rit not in 5,7-DHT-lesioned rats. In Experiment 2, a second method for depl eting 5-HT was used. The tryptophan hydroxylase inhibitor p-chlorophenylala nine (PCPA) also disrupted PPI without altering basal startle reactivity. A gain, 8-OH-DPAT disrupted PPI in control animals; this effect was not alter ed in PCPA-treated also but the increase in basal startle reactivity induce d by 8-OH-DPAT tons not observed in PCPA-treated rats. Taken together with the results of previous experiments involving drugs that enhance 5-HT neuro transsmission it appears that both increases and decreases in 5-HT activity disrupt PPI. (C) 2001 American College of Neuropsychopharmacology Publishe d by Elsevier Science Inc.