"Typical" but not "atypical" antipsychotic effects on startle gating deficits in prepubertal rats.
BACKGROUND
Dopamine (DA) agonists and NMDA antagonists disrupt sensorimotor gating in rats, as measured by a loss of prepulse inhibition of the startle reflex. These effects are used in predictive models for antipsychotic efficacy: clinically "typical" and "atypical" antipsychotics restore PPI in adult rats treated with DA agonists such as apomorphine (APO), while clinically "atypical" antipsychotics restore PPI in rats treated with NMDA antagonists such as phencyclidine (PCP). We previously reported that the PPI disruptive effects of both APO and PCP are evident in 16- to 18-day-old rat pups, suggesting that the brain substrates for these effects are functional very early in development.


OBJECTIVE
In the present study we assessed the developmental patterns of antipsychotic effects in these measures.


METHODS
The PPI-disruptive effects of APO and PCP, and their antagonism by the typical antipsychotic haloperidol, and the atypical antipsychotic quetiapine, were assessed across development in Sprague-Dawley rats.


RESULTS
Similar to the pattern seen in adults, both haloperidol and quetiapine opposed APO-induced PPI deficits in 16- to 19-day-old rat pups. However, the "atypical" antipsychotic quetiapine did not oppose PCP-induced PPI deficits in pups or prepubertal (45 day) adolescents, but did oppose these PCP effects in postpubertal rats.


CONCLUSIONS
While brain substrates mediating the PPI-disruptive effects of DA agonists and NMDA antagonists are functional early in development, some physiological event associated with puberty is a necessary condition for the "atypical antipsychotic profile" in this predictive model.
Martinez
Zoë A
ZA
Department of Psychology, University of California, Los Angeles, USA.
Platten
Amanda
A
Pollack
Erica
E
Shoemaker
Jody
J
Ro
Hyun
H
Pitcher
Leia
L
Geyer
Mark A
MA
Swerdlow
Neal R
NR
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001058:Apomorphine / Q000494:pharmacology; D003987:Dibenzothiazepines / Q000494:pharmacology; D005260:Female; D010622:Phencyclidine / Q000494:pharmacology; D000069348:Quetiapine Fumarate; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D013216:Reflex, Startle / Q000187:drug effects*; D012741:Sexual Maturation / Q000502:physiology*
D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D016194:Receptors, N-Methyl-D-Aspartate; D000069348:Quetiapine Fumarate; D010622:Phencyclidine; D001058:Apomorphine