Regional localization of [14C]mescaline in rabbit brain after intraventricular administration

Albino rabbits of either sex were anesthetized, and a cannula was implanted permanently into the lateral ventricle. About 1 week later, the distribution of ¹⁴C]mescaline and its deaminated metabolite, ¹⁴C]trimethoxyphenylacetic acid (¹⁴C]TMPA) in 12 brain regions was examined at 15, 60, and 180 min after the intraventricular injection of ¹⁴C]mescaline (0.5 mol in 0.05 ml saline).¹⁴C-radioactivity was rapidly distributed in all regions, reaching peak levels within 15 min. The spinal cord, superior colliculus, pons, hypothalamus, caudate, medulla oblongata, and inferior colliculus contained 23–57 nmol/g of mescaline; the thalamus, tegmentum, and cerebellum, 12–15 nmol/g; and the cerebrum and hippocampus, less than 10 nmol/g; the levels of ¹⁴C]TMPA ranged from 0.5 to 5 nmol/g. The levels of ¹⁴C]mescaline and of ¹⁴]TMPA in all brain areas were considerably decreased 180 min after its injection. Pretreatment with chlorpromazine (15 mg/kg, i.p., 30 min) lowered ¹⁴C]mescaline concentrations in the hippocampus, caudate, thalamus, and cerebrum and elevated them in the spinal cord, medulla oblongata, pons, and tegmentum; ¹⁴C]TMPA levels as the percentage of total radioactivity were not affected. Pretreatment with iproniazid (150 mg/kg, i.p., 18 h), on the other hand, uniformly reduced the TMPA levels in all brain areas, with the resultant increases in mescaline levels. The CPZ-effect in lowering the mescaline concentrations in the areas belonging to the limbic system may have significance in explaining its antihallucinogenic effect in humans and its ability to block the altered behavior induced by the latter drug in laboratory animals.