EFFECT OF PENTYLENETETRAZOL ON THE EXPRESSION OF TYROSINE-HYDROXYLASEMESSENGER-RNA AND NOREPINEPHRINE AND DOPAMINE TRANSPORTER MESSENGER-RNA

Seizure activity has been shown to have differential effects on the te rminal content of the monoamines, norepinephrine (NE) and dopamine (DA ). Induction of seizure activity reduces the terminal content of NE, w hile DA levels remain unchanged or slightly elevated. This study exami ned the effect of the chemoconvulsant pentylenetetrazol (PTZ) on the m RNA expression of regulatory proteins which maintain the terminal cont ent of NE and DA (i.e., synthesis and re-uptake). The areas examined w ere the noradrenergic neurons of the locus coeruleus (LC) and dopamine rgic neurons of the substantia nigra pars compacta/ventral tegmentum a rea (SNpc/VTA) in the rat. In the LC, PTZ increased mRNA expression of the immediate early gene, c-fos, and mRNA expression of the synthesiz ing enzyme, tyrosine hydroxylase (TH), and the re-uptake protein, nore pinephrine transporter (NET). This effect on TH and NET was observed o nly 1 day after the administration of PTZ. In contrast, PTZ did not al ter the expression of c-fos mRNA in the SNpc/VTA, but reduced the expr ession of the dopamine transporter (DAT) mRNA. This effect was observe d only 1 day after the administration of PTZ. TH mRNA expression in do paminergic neurons was elevated initially in a manner similar to that observed in the LC. However, the effect of PTZ on TH mRNA expression i n dopaminergic neurons was more prolonged (still elevated 3 days later ). These results indicate that the chemoconvulsant PTZ has differentia l effects on the mRNA expression of regulatory systems (TH and neurotr ansporter proteins) in noradrenergic and dopaminergic neurons.