No abstract

There is now substantial evidence that several TIQs and beta-carbolines are present in vivo and increase during certain pathological conditions. It still remains to be determined, however, precisely what roles they play in endogenous functions and whether or not they are critical for the expression of these pathological conditions. Accumulating biochemical information continues to support the notion that these compounds can act as false transmitters. The exciting new findings, which will certainly receive a great deal more attention, concern the interaction of some of the beta-carbolines with the benzodiazepine receptor. Determining if a beta-carboline is an endogenous receptor ligand will attract further research interest on the theoretical and specifically clinically-directed levels. Biochemical, morphological, and behavioral data indicate that some of the condensation products can act as neurotoxins. Very few experiments have included an examination of long-term effects of exposure to one of these alkaloids, so the amount of information on this issue is limited. Chronic rather than acute administration of an alkaloid is more likely to mimic the pathological states in which these compounds are hypothesized to play a role. Biochemically, both the dopaminergic and serotonergic systems have been shown to be affected by chronic treatments with certain alkaloids. Progressive and long-term behavioral alterations also have been reported. Such changes may reflect an adaptation to an increase or decrease in activity of particular systems or a neurotoxic action.

Tetrahydropapaveroline (THP), a dopamine-dopaldehyde condensation product, was delivered directly into the cerebral ventricle of rats automatically every 15 minutes for 12 days. The animals were given access to both water and ethylalcohol, the latter being presented in 12 concentrations from 3 to 30 percent. Within 3 to 6 days of the start of the infusion of THP, the rats, which normally rejected alcohol, drank alcohol solutions in increasingly excessive amounts; this was accompanied by symptoms that were similar to those of withdrawal and intoxication. These results provide evidence that an abnormal metabolite in the brain may produce the addictive state caused by alcoholic beverages.

No abstract