Effects of baclofen and gamma-hydroxybutyrate on rat striatal and mesolimbic 5-HT metabolism.

The effects of D, L-baclofen and gamma-hydroxybutyric acid (GHBA) on endogenous 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in the rat striatum and the mesolimbic area were investigated and compared with their effects on dopamine (DA) concentrations in the same regions. Both baclofen (5-50 mg/kg i.p.) and GHBA (300--1500 mg/kg i.p.) led to dose-dependent increases in the striatal levels of 5-HT and 5-HIAA by up to 200%. Maximal effects of both drugs occurred about 3 h after treatment. Normalization was reached 6 h after GHBA and 16 h after baclofen. The effect of GHBA in the mesolimbic area was qualitatively similar to, but weaker than, its effect in the striatum. Baclofen had little or no effect in the mesolimbic area, the cortex or the brain stem. The two drugs affected striatal 5-HT and DA metabolism similarly. Their effects on the latter are thought to be due to cessation of impulse flow. The effects on striatal 5-HT may be related to more complex phenomena.