Abstract

We here report on behavioral effects of neonatal medial prefrontal cortex (mpfc) lesions in rats, followed by chronic peripubertal treatment with the cannabinoid full agonist WIN 55,212-2 (WIN). Rat pups received excitotoxic lesions of the mpfc on postnatal day (pd) 7. Chronic WIN (1.2 mg/kg) treatment was extended throughout the rats' puberty (pd 40-65). All animals were tested as juveniles and adults for short-term memory functioning using the spontaneous object recognition test, and for locomotor activity in an open field. Lesioned rats showed impairments in recognition memory when tested prepubertally. Postpubertal testing of lesioned animals revealed a persisting recognition memory impairment that was intensified by pubertal WIN treatment. Chronic WIN treatment during puberty also affected recognition memory in sham-lesioned rats and controls. No effects on locomotor activity of either neonatal lesion or pubertal cannabinoid treatment were found. This study shows that behavioral deviations induced by neonatal mPFC lesions can be exacerbated by pubertal chronic cannabinoid treatment, leading to long-lasting impairments of mnemonic short-term information processing.