Distinct sites of dopaminergic and glutamatergic regulation of haloperidol-induced catalepsy within the rat caudate-putamen

Previous studies have indicated that corticostriatal glutamatergic pathways are implicated in the regulation of neuroleptic catalepsy. To obtain a better understanding of the way in which dopamine (DA) and glutamate interact within the caudate-putamen (CP) in the development of catalepsy, we investigated the regional distribution within the rat CP of the cataleptogenic effect of haloperidol and its antagonism by d(−)-2-amino-5-phosphonopentanoic acid ( d(−)AP5), a selective antagonist of the N-methyl- d-aspartate (NMDA) glutamate receptor subtype. Bilateral injections of haloperidol (3 μg/side) into the rostral ventromedial (VM) CP induced potent catalepsy with a short latency after the injection. In contrast, only a weak cataleptic response, of slower onset, was observed after haloperidol injections into the rostral ventrolateral (VL), rostral dorsomedial (DM), or rostral dorsolateral (DL) CP, or into the nucleus accumbens. d(−)AP5 (5 μg/side) injected bilaterally into the dorsorostral CP (DM and DL) strongly inhibited the catalepsy induced by systemic haloperidol (1 mg/kg, i.p.), and this effect lasted longer when the drug was injected into the DM than when it was injected into the DL. d(−)AP5 did not affect haloperidol-induced catalepsy when injected into the ventrorostral (VM and VL) or intermediate dorsal CP. d(−)AP5 injected into the DM, the region most sensitive to the anticataleptic effect of the drug, had no effect on basal levels of DA and its metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, or on the modification of these levels by haloperidol in either the DM or VM. These findings suggest that, while the catalepsy resulting from DA receptor blockade by haloperidol originates mainly from the VM, the expression of this phenomenon depends on an intact glutamatergic transmission within the dorsorostral CP. In the development of neuroleptic catalepsy, the mesencephalostriatal DAergic and corticostriatal glutamatergic pathways seem to be functionally linked through an indirect, rather than a direct, interaction.