Cocaine and d-amphetamine increase c-fos expression in the rat cerebellum

Psychostimulant drugs have been reported to increase the expression of some immediate-early genes in the cerebellum. In the present study, immunohistochemical techniques were used to assess the pattern of c-fos expression in the cerebellum produced by d-amphetamine or cocaine. Systemic administration of d-amphetamine (1.5, 6 mg/kg) or cocaine (10, 20 mg/kg) increased locomotor activity, which at low doses was blocked by pretreatment with the dopamine D1 receptor antagonist SCH 23390 (1 mg/kg). Within the cerebellum, basal levels of c-fos expression were abolished by SCH 23390, with the exception of lobule VI. Dose-dependent increases in Fos-like immunoreactivity were elicited by d-amphetamine and cocaine. Pretreatment with SCH 23390 greatly reduced the extent to which either stimulant increased c-fos expression. Psychostimulant-induced Fos-like immunoreactive nuclei were generally restricted to the granule cell layer within each of the midvermal cerebellar lobules (I-X), although occasional nuclei were found in the Purkinje cell layer. In addition, a homogeneous pattern of Fos-like immunoreactive nuclei, of sparse density, was also found near the pial surface of the molecular layer following d-amphetamine but not cocaine. Within the granule cell layer dense clusters of Fos-like immunoreactive neurons extended from the molecular layer to the Purkinje cell layer and were found at both the pial surface as well as in the deep portions of individual folia. These data add to a growing body of evidence indicating that the induction of regionally specific alterations in c-fos expression by psychostimulants is mediated via a D1 receptor mechanism.