Effects of phencyclidine and phencyclidine biologs on sensorimotor gating in the rat*1

Clinical and Sensorimotor Gating Effects of Ketamine in Normals

“…On the contrary, ketamine produced a significant enhancement of gating as indicated by increases in percent prepulse inhibition in Block 1 of the startle session. This is contrary to the disruptions in gating which have been reported in animals treated with PCP, ketamine, and MK-801 (Mansbach and Geyer 1989;Mansbach 1991;Keith et al 1991;Swerdlow et al 1993;Johansson et al 1995;al-Amin and Schwartzkopf 1996;Swerdlow et al 1998;de Bruin et al 1999).…”

“…Schizophrenics have impairments in PPI (Braff et al 1978;Braff et al 1992;Grillon et al 1992;Bolino et al 1994;Parwani et al 2000). PPI is similarly impaired in animals following treatment with the NMDA antagonists PCP, MK-801, or ketamine (Mansbach and Geyer 1989;Mansbach 1991;Keith et al 1991;Swerdlow et al 1993;Johansson et al 1995;al-Amin and Schwartzkopf 1996). However, PPI changes in animals treated with ketamine appear to be variable depending on timing and dose of ketamine administered (Mansbach and Geyer 1989;Mansbach 1991;Johansson et al 1995;Swerdlow et al 1998;de Bruin et al 1999).…”

Oxytocin as a natural antipsychotic: a study using oxytocin knockout mice

“…41 With regard to PPI, specifically, the findings in healthy patients are mixed, with one study reporting disruption of 'PPI-like' auditory gating following treatment with ketamine, 42 some studies reporting no effects of ketamine on PPI, 43,44 and others reporting enhancement of PPI. [45][46][47] However, it is clear that patients with schizophrenia do have altered PPI 1,5,[48][49][50] and that in nonhuman primates 51,52 and rodents, [53][54][55][56] treatment with NMDA antagonists disrupts PPI. Why there are discrepancies in the effects of NMDA antagonists on PPI between clinical and preclinical studies remains unknown.…”

Galantamine and donepezil attenuate pharmacologically induced deficits in prepulse inhibition in rats

“…For the scopolamine-reversal studies, scopolamine HBr (Sigma S1875) 0.33 mg/kg was administered 40 min before testing followed by either vehicle or AChEI 20 min before testing. The PPI methods and the compounds used to disrupt PPI (and their doses) were based on earlier studies (Mansbach et al, 1988;Mansbach and Geyer, 1989;Jones and Shannon, 2000b) and recent work in our laboratory (Terry et al, 2005). Galantamine was tested at doses of 0.3, 1.0, and 3.0 mg/kg while donepezil doses were 0.5, 1.0, and 2.0 mg/kg.…”

“…Accordingly, a number of animal models of PPI impairment have been developed which include neonatal ventral hippocampal lesion, maternal deprivation, isolation rearing, genetic, and pharmacological models, the later being commonly used in antipsychotic drug development studies . Such pharmacological models have provided evidence that the neurotransmitters dopamine (Mansbach et al, 1988), glutamate (Mansbach and Geyer, 1989), serotonin (Sipes and Geyer, 1994), and acetylcholine (Jones and Shannon, 2000), are each likely to play an important role in normal sensory gating and PPI as well as disorders of these processes.…”