Effects of amphetamine and cocaine treatment on c-Fos, Jun-B, and Krox-24 expression in rats with intrastriatal dopaminergic grafts

Activation of dopaminergic (DA) transmission by psychostimulants increases c-fos expression. d-Amphetamine-induced c-fos activation is reduced in the neostriatum deprived of DA afferents. Dopaminergic grafts implanted into th e denervated neostriatum induce a c-fos hyperexpression when challenged wit h d-amphetamine, which is correlated with the exaggerated compensation of d -amphetamine-induced rotation. The aim of the present study was to test the generality of this phenomenon and the effects of DA grafts on the expressi on of three immediate early gene-coded proteins (c-Fos, Jun-B, Krox-24) fol lowing a challenge with either d-amphetamine or cocaine. c-fos basal expres sion was low in the neostriatum and was increased by the administration of psychostimulants. These effects were blocked by the DA lesion and restored by the DA grafts. A c-fos hyperexpression was observed within the grafted n eostriatum, which was correlated with the compensation of d-amphetamine- or cocaine-induced rotation. Basal levels of Jun-B- and Krox-24-LI nuclei wer e high within the neostriatum. Administration of d-amphetamine or cocaine d id not influence the expression of these IEG-coded proteins. Jun-B expressi on was not affected by the surgical procedure. In contrast, lesion of DA af ferents of neostriatum decreased Krox-24 basal expression, an effect revers ed by the grafts. Thus, the expression of c-fos but not Jun-B or Krox-24 ap peared to be a good marker for the rotational behavior exhibited by DA-graf ted rats challenged with drugs that increased DA transmission. This general ized c-fos overshoot indicates an abnormal activation of postsynaptic neuro ns by dopamine and points to its value as an indicator of the deleterious e ffects of DA grafts. (C) 1999 Academic Press.