The effects of dentate granule cell destruction on behavioural activity and Fos protein expression induced by systemic methamphetamine in rats

1 We destroyed dentate granule cells unilaterally or bilaterally by means o f intrahippocampal injection of colchicine in rats. Subsequently, we observ ed behavioural changes following the intraperitoneal injection of 2 mg kg(- 1) methamphetamine or saline, in addition to quantitatively assessing Fos p rotein expression in several brain regions, including the medial prefrontal cortex, cingulate cortex, piriform cortex, dorsal striatum, and nucleus ac cumbens. 2 Bilaterally lesioned animals, when administered saline, showed a marked i ncrease in locomotor activity compared with those of non-lesioned animals. With respect to the methamphetamine response, bilateral destruction resulte d in a marked enhancement of locomotor activity, while the unilateral destr uction led to a marked increase in rotation predominantly contralateral to the lesioned side, with no identifiable change in locomotor activity. 3 Bilaterally lesioned animals, when administered saline and having undergo ne an immunohistological examination, showed a marked increase in Fos expre ssion in both sides of the nucleus accumbens. Bilaterally lesioned animals administered methamphetamine showed a marked increase in Fos expression in the right and left sides of all regions tested. Unilaterally lesioned anima ls administered methamphetamine showed a significant and bilateral enhancem ent in Fos expression in the medial prefrontal and cingulate cortices, and a marked and unilateral (ipsilateral to the lesioned side) enhancement of F os protein in the piriform cortex, dorsal striatum, and nucleus accumbens. 4 The present findings suggest that dentate granule cells regulate methamph etamine-associated behavioural changes through the function of widespread a reas of the brain, mostly the nucleus accumbens.