The Effects of Substance P After Central Administration on the Activity of the Mesolimbic System of the Rat Brain as Studied by Microdialysis

In vivo microdialysis was used to study the effects of substance P on dopamine, dihydroxyphenylacetic acid, and homovanillic acid levels in the nucleus accumbens in rats. Each animal received sequential injections of physiological saline, 0.1 μg of substance P, and 1 μg of substance P into the lateral ventricle over three days. Dialysates showed increases in dopamine levels in response to neuropeptide, by 41% for the 0.1 μg dose and 71% for the 1 μg dose. The dynamics of these changes also depended on the concentration of the agent. Administration of 1 μg of substance P gave a peak dopamine level at 50 min; the neurotransmitter level remained significantly elevated 75 min after dosage with substance P. The dopamine level was increased only at 75 min when the 0.1 μg dose of neuropeptide was used. Changes in metabolite levels were also dose-dependent. After the 1 μg dose, the dihydroxyphenylacetic acid level increased by 28%, while the 0.1 μg dose produced no significant change in the level of this metabolite. The homovanillic acid level did not respond to administration of substance P at either dose. These data support the suggestion that the influence of substance P on the internal compensation system is to a significant extent mediated by dopaminergic mechanisms and provides a possible explanation for the effects of the neuropeptide seen in a conditioned place preference reflex.