Evidence that a preferred substrate for type B monoamine oxidase mediates stimulus properties of MAO inhibitors: a possible role for beta-phenylethylamine in the cocaine cue.

In the experiment, rats were trained to discriminate 5 mg/kg cocaine HCl from saline in a two-bar drug discrimination procedure. Stimulus generalization experiments were carried out with six inhibitor drugs of monoamine oxidase. The rank order of absolute potency of these drugs in inducing stimulus generalization with cocaine was: tranylcypromine (ED50 in mg/kg; 1.2)>pheniprazine (3.5)>deprenyl (5)>pargyline (28)>nialamide (approximately 170); at up to 40 mg/kg, clorgyline failed to produce 50% generalization. All six drugs also potentiated tryptamine in producing body tremors and clonic seizures, the rank order of potency being tranylcypromine (0.081)>clorgyline (0.14) greater than or equal to pheniprazine (0.15)>pargyline (1.97)>deprenyl (15.5)>nialamide (18.7). Tryptamine is a common substrate for both type A and type B monoamine oxidase, so that tryptamine potentiation may serve to determine the relative specificity of the doses at which the inhibitor drugs generalized with cocaine. The present data may suggest that endogenous substances which are preferred substrates for type B monoamine oxidase in rat brain can exert control of behavior by virtue of cocaine-like stimulus properties. beta-Phenylethylamine, more so than dopamine, appears to be candidate substance for mediating the discriminative stimulus properties of cocaine and, perhaps, of other central nervous system stimulants.