Interaction of cholecystokinin and diazepam: effects on brain monoamines

Summary— An antagonism between cholecystokinin (CCK) peptides and benzodiazepines (BZD) has been described in various paradigms. We sought to determine whether CCK and BZD are also antagonistic in their effects on brain neurotransmitter levels in the rat. No effect on the noradrenergic system was induced in any brain area by CCK 8 S and diazepam alone or in combination. Administered alone, sulfated CCK octapeptide (CCK 8 S) (5 μg/kg ip) and diazepam (5 mg/kg ip) were found to decrease DOPAC levels in the cortex and to induce 5-hydroxy-tryptamine accumulation in the hippocampus. When administered together, these variations were no longer observed. However, a slight tendency by each substance to decrease 3-methoxy-tyramine levels in the striatum, became significant when given in association. The differences in CCK-BZD interactions observed in the striatum, cortex and hippocampus suggest that different mechanisms of action are involved. The addition of the effects occuring in the striatum might involve a GABA-ergic mechanism.