Behavioral alterations induced by formaldehyde-derived tetrahydroisoquinolines

Rats administered intracerebroventricular (IVT) injections of 3-Carboxy-1,2,3,4-tetrahydroisoquinoline (I) or 6,7-Dihydroxy-1,2,3,4-tetrahydroisoquinoline (II), the condensation products of formaldehyde with phenylalanine and dopamine, respectively, were evaluated in the open field and shuttle box situation. In the open field, 45 min after the acute administration of I, several repetitive purposeless responses and other manifestations such as teeth chattering, wet dog shakes and stiffness of the tail were observed; however, no quantitative effects were detected in the behavioral parameters recorded. Further studies were performed utilizing the shuttle box situation with drugs I and II. They produced an increase in the number of escapes and latency of shocks when measured 45 min after IVT administration (10 mg/ml and 1 mg/ml, respectively; 20 microliters). Our data suggest that the studied compounds induce qualitative alterations as well as changes in shuttle avoidance behavior in the rat when measured 45 min after administered. The effects were found to be dose and time dependent, being reversible when measured 24 and 48 hours after administration of the drugs. The present results open the possibility that the in vivo formation of tetrahydroisoquinolines could be involved in some mental pathologies, such as schizophrenia, as has been previously suggested.