Loss of Parvalbumin in the Hippocampus of MAM Schizophrenia Model Rats Is Attenuated by Peripubertal Diazepam

Abstract

Background: Loss of parvalbumin interneurons in the hippocampus is a robust finding in schizophrenia brains. Rats exposed during embryonic day 17 to methylazoxymethanol acetate exhibit characteristics consistent with an animal model of schizophrenia, including decreased parvalbumin interneurons in the ventral hippocampus. We reported previously that peripubertal administration of diazepam prevented the emergence of pathophysiology in adult methylazoxymethanol acetate rats.

Methods: We used an unbiased stereological method to examine the impact of peripubertal diazepam treatment on parvalbumin interneuron number in the ventral subiculum, dentate gyrus of the hippocampus and the basolateral amygdala.

Results: Methylazoxymethanol acetate rats with peripubertal diazepam showed significantly more parvalbumin interneurons (3355±173 in the ventral subiculum, 1211±76 in the dentate gyrus) than methylazoxymethanol acetate without diazepam (2375±109 and 824±54, respectively). No change was found in the basolateral amygdala.

Conclusions: Peripubertal diazepam attenuated the decrease of parvalbumin in the ventral hippocampus of methylazoxymethanol acetate rats.

Keywords: animal model; diazepam; parvalbumin interneuron; schizophrenia.

Figure 1.

The loss of parvalbumin interneurons in methylazoxymethanol acetate (MAM) rats was attenuated by peripubertal diazepam administration. (a) Images of ventral subiculum (vSub) from saline (Sal), MAM, and MAM: diazepam (DZ) animals; scale bar = 100 μm. Boundaries of the counting area, pyramidal cell layer of vSub, are delineated by dotted lines. (b) Example image of parvalbumin interneurons. Arrows point to parvalbumin cells in focus; scale bar = 10 μm. (c) MAM rats exhibited a significantly lower number of parvalbumin interneurons in the vSub; however, MAM rats with peripubertal administration of diazepam (MAM:DZ) showed a significantly higher number of parvalbumin interneurons in the vSub compared with MAM:Veh rats, although the number is still significantly lower compared with Sal:Veh and Sal:DZ rats. *P<. 05; ***P<. 001. (d) In the hilus of the ventral DG, MAM:Veh rats showed a significantly lower number of parvalbmin interneurons than Sal:Veh, which was significantly attenuated in the MAM:DZ rats. Sal:DZ rats showed a significantly lower PV number than Sal:Veh rats. (e) The number of parvalbumin interneurons in the basolateral amygdala (BLA) did not differ significantly between Sal and MAM rats.