Effects of phencyclidine on acoustic startle and prepulse inhibition in neuronal nitric oxide synthase deficient mice.
Prepulse inhibition of acoustic startle is a behavioural response, which is used to estimate sensorimotor gating deficits in schizophrenia. Recent studies show that several behavioural effects of the psychotomimetic drug, phencyclidine (PCP), in rodents are blocked by nitric oxide synthase (NOS) inhibitors suggesting that NO plays an important role in the pharmacological effects of PCP. The present study was conducted to examine the effects of PCP on prepulse inhibition in neuronal NOS (nNOS) deficient mice. PCP treatment caused a significant and dose-related increase in prepulse inhibition in nNOS-/- mice whereas prepulse inhibition was not significantly affected in +/+ and +/- mice. Basal prepulse inhibition level did not differ significantly between the groups. Furthermore, PCP caused a dose-related decrease in startle response reactivity in +/+ mice but did not significantly affect this measure in +/- and -/- mice. Basal startle response level did not differ between +/+ and +/- but was significantly lower in -/- mice. It is concluded that nNOS plays a role in the NO-sensitive effects of PCP.
Klamer
Daniel
D
Department of Pharmacology, The Sahlgrenska Academy at Göteborg University, POB 431, SE 405 30 Göteborg, Sweden.
Engel
Jörgen A
JA
Svensson
Lennart
L
D000818:Animals; D004305:Dose-Response Relationship, Drug; D006579:Heterozygote; D006720:Homozygote; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D010622:Phencyclidine / Q000494:pharmacology*; D013216:Reflex, Startle / Q000187:drug effects*
D010622:Phencyclidine