Developmentally Vitamin D Deficient Rats Show Enhanced Prepulse Inhibition after Acute ∆ Running Title: Developmental Vitamin D Deficiency and Thc

Rationale: Developmental vitamin D (DVD) deficiency has been proposed as a risk factor for schizophrenia. DVD-deficient rats show selective cognitive deficits and novelty-induced hyperlocomotion, and enhanced locomotor responses from acute treatment with psychomimetic drugs, such as amphetamine and MK-801. Here we wished to examine the effect of a drug from a different class of psychomimetic/psychoactive compounds, ∆ 9-tetrahydrocannabinol (THC), on tasks with relevance to the cognitive and positive symptoms of schizophrenia. Objectives: The aim of this study was to investigate whether DVD deficiency modulates the behavioural effects of THC on tests of delay-dependent memory, sensorimotor gating and locomotion. 1.25, 2.5 mg/kg) 15 min before a delay match to sample task (DMTS) using variable delays (0-24 s). A separate group of rats were injected with either 2.5 mg/kg THC or vehicle before tests of either prepulse inhibition (PPI) of the acoustic startle response (ASR) or in the open field. Results: Control and DVD-deficient rats showed a similar dose-dependent impairment in performance on the DMTS. The greatest impairment was seen at 2.5 mg/kg at all delays (0-24s). DVD-deficient rats displayed THC-induced enhancement of PPI, which was not seen in control rats. There was no effect of maternal diet on ASR or locomotor responses in the open field. Conclusions: This study reports the novel findings that DVD-deficient rats were more sensitive to the acute effects of THC on PPI. It appears that prenatal vitamin D deficiency has long-term effects on the sensitivity to the behavioural effects of cannabinoids.