In the light of current reports that capsaicin depletes substance P from spinal neurones, this compound has been investigated as a possible tool with which to manipulate supraspinal substance P systems. Capsaicin (30 μg) was dissolved in dimethyl sulphoxide (DMSO) and injected bilaterally into the pars reticulata of the rat substantia nigra. Capsaicin-injected rats showed enhanced locomotor activity up to 6 days after surgery when compared to the DMSO sham-injected control animals. The injection of capsaicin greatly reduced the cataleptic effects of fluphenazine (1.5 mg/kg) on day 1 after surgery. Biochemically no changes in substance P content in the nigra were detected after intranigral injection of capsaicin. However, nigral concentrations of 5-hydroxytryptamine (5-HT) and its metabolite 5-hydroxyindoleacetic acid were significantly decreased on days 1 and 3 after capsaicin injection. No other changes in concentrations of putative nigral transmitter candidates were observed, although a significant increase in the levels of the metabolites of dopamine was measured in both the striatum and nucleus accumbens on days 1 and 3 after intranigral capsaicin injection. By day 8 all behavioural and biochemical measurements were similar in capsaicin- and DMSO-injected rats.

In conclusion, capsaicin does not seem to be a useful tool with which to deplete substance P containing neurones in the nigra. It is suggested that the enhanced locomotor effects observed after injection of this agent may be related to the depletion of nigral 5-HT systems and the subsequent enhancement of striatal and nucleus accumbens dopamine metabolism, although the possible effects of capsaicin on efferent motor pathways from the substantia nigra should not be overlooked.