TREATMENT WITH ACTH(4-10) ANALOG (BIM-22015) REDUCES FUNCTIONAL AND ANATOMICAL IMPAIRMENTS FOLLOWING MEDIAL FRONTAL-CORTEX ABLATION IN RAT

Adult rats with bilateral medial frontal cortex lesions were given inj ections of either sterile water or 1, 10, 100, or 1000 mug/kg of an AC TH4-10 analog (BIM-22015) every other day for 28 days after surgery. S even days after surgery the rats were tested on a spatial navigation t ask for ten days (2 trials/day). Repeated measures ANOVA revealed a si gnificant difference between the groups on time (p < 0.05) and distanc e (p < 0.05) to locate the escape platform over the 10 days of acquisi tion. Post-hoc analyses indicated that in the rats with frontal cortex lesions, the 1 mug/kg dosage improved water maze acquisition as compa red to lesion-only controls (p < 0.05). No significant effects of lesi on or treatment were found for retention tests conducted 10 days follo wing acquisition. Fifty-six days after surgery the rats were given one week of pretraining, followed by acquisition testing, on a T-maze tes t of delayed spatial alternation learning. No group differences for nu mber of days to criterion, errors, or perseverations were found on thi s task. Histological analyses showed the lesions were restricted to th e anterior portions of the medial frontal cortex. These overall findin gs are in agreement with those of Silva et al. (1), who reported that small medial frontal lesions do not cause spatial alternation deficits in a T-maze. Rats with the 1mug/kg treatments had significantly more AChE-positive neurons in the nucleus basalis magnocellularis (NBM) tha n lesion controls.