Abstract
These experiments examined the impact of extensive depletions of forebrain 5-hydroxytryptamine (5-HT; serotonin) levels on prepulse inhibition (PPI) of the acoustic startle reflex in rats. In Experiment 1, injection of the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) into the dorsal and median raphe nuclei disrupted PPI. This deficit was observed beginning 2 days after lesioning 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 dopamine receptor agonist apomorphine (1mg/kg) also disrupted PPI; the effect of 8-OH-DPAT, but not apomorphine, was potentiated in 5-HT-depleted rats. Basal startle reactivity was enhanced by 8-OH-DPAT in sham-lesioned rats but not in 5,7-DHT-lesioned rats. In Experiment 2, a second method for depleting 5-HT was used. The tryptophan hydroxylase inhibitor p-chlorophenylalanine (PCPA) also disrupted PPI without altering basal startle reactivity. Again, 8-OH-DPAT disrupted PPI in control animals; this effect was not altered in PCPA-treated rats but the increase in basal startle reactivity induced by 8-OH-DPAT was not observed in PCPA-treated rats. Taken together with the results of previous experiments involving drugs that enhance 5-HT neurotransmission it appears that both increases and decreases in 5-HT activity disrupt PPI.
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Acknowledgements
This work was supported by an operating grant from the Medical Research Council of Canada to PJF and TLS. PJF is a Career Scientist of the Ontario Ministry of Health.
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Fletcher, P., Selhi, Z., Azampanah, A. et al. Reduced Brain Serotonin Activity Disrupts Prepulse Inhibition of the Acoustic Startle Reflex: Effects of 5,7-dihydroxytryptamine and p-chlorophenylalanine. Neuropsychopharmacol 24, 399–409 (2001). https://doi.org/10.1016/S0893-133X(00)00215-3
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DOI: https://doi.org/10.1016/S0893-133X(00)00215-3
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