NO-mediated cGMP synthesis in cholinergic neurons in the rat forebrain: effects of lesioning dopaminergic or serotonergic pathways on nNOS and cGMP synthesis

Nitric oxide synthase (NOS) activity and NO-mediated cGMP synthesis were st udied in the rat forebrain of control animals and animals which had receive d a unilateral lesioning of dopaminergic or serotonergic pathways. Lesionin g of the dopaminergic innervation using 6-hydroxydopamine resulted in a 50% decrease in NOS activity in the lesioned frontal cortex and caudate putame n. Lesioning of the serotonergic innervation using 5,7-dihydroxytryptamine had no effect on NOS activity. NO-mediated cGMP accumulation in rat forebra in slices was not affected by 6-hydroxydopamine or 5,7,-dihydroxytryptamine lesioning. Using cGMP immunocytochemistry, it was demonstrated that NO-med iated cGMP synthesis was absent from dopaminergic, serotonergic, GABA-ergic and neuronal NOS-containing nerve fibres. A minor colocalization of cGMP i mmunoreactivity was found in parvalbumin-containing fibres in the cortex. E xtensive colocalization between cGMP immunoreactivity and the acetylcholine transporter was found in all cortical areas and in the caudate putamen. Th ere was no effect of the lesions on this colocalization. These results demo nstrate NO-mediated cGMP accumulation in cholinergic fibres in the forebrai n of the rat and suggest an anterograde signalling function of NO in cholin ergic neuronal systems in the cortex and caudate putamen of the rat.