Stress and Strain and Sensorimotor Gating

Abstract

Strain differences in sensitivity to dopaminergic effects on sensorimotor gating have been used to study the genetic basis of schizophrenia. Corticotropin releasing hormone (CRF), a major mediator of stress effects, also regulates PPI and may be involved in the mechanism by which stress causes onset or relapse of schizophrenia. This study examined whether Sprague Dawley rats from different vendors exhibit equivalent sensitivity to CRF effect on prepulse inhibition of acoustic startle response (PPI). The effect of centrally-administered human/rat CRF (1.0 or 3.0 μg, icv) on percent PPI was assessed in male Sprague Dawley rats from Harlan (San Diego, CA) and from Charles River Laboratories (CR; Wilmington, MA) 40 min and 24 h after CRF infusion. Independent of effect on mean startle, the highest dose of CRF produced a disruption in PPI in Harlan rats 40 min after infusion, while neither dose produced an effect in CR rats. No effect was observed in either sub-strain 24 h after CRF infusion. Next, we tested the effect of a subthrehold dose of quinpirole (0.05 mg/kg), a D2-like receptor agonist, in combination with centrally administered CRF (3.0 μg) on PPI. Neither quinpirole alone nor or in combination with CRF disrupted PPI in CR rats. The results demonstrate that sensitivity to CRF varies across sub-strains of Sprague Dawley rats, with those from Harlan San Diego being most prone to CRF-induced PPI disruption. This sub-strain is known to be more sensitive to dopaminergic disruption of PPI than Long-Evans rats, but enhancing D2-agonist stimulation does not seem to confer CRF sensitivity. Nevertheless, such differences in the sensitivity to PPI-disruptive effects of CRF could be exploited to investigate the neurobiological basis of vulnerability to stress.