Neuropsychobiology 5: 327-331 (1979) Page 1 of 1 Effect of Benztropine on Haloperidol-Induced Prolactin Secretion 1 S. Lal, T. Mendis, P. Cervantes, H. Guyda and J.L. De Rivera Departments of Psychiatry, Montreal General Hospital and McGill University; Douglas Hospital, and Protein and Polypeptide Laboratory, Montreal, PQ Key Words. Prolactin  Cholinergic mechanisms  Benztropine  Haloperidol Abstract. The effect of benztropine on haloperidol-induced prolactin secretion was investigated in 10 normal male volunteers. Benztropine had no. effect on basal prolactin secretion but significantly enhanced the increase induced by haloperidol. The magnitude of the enhancement, however,. was relatively small. These data suggest that in man cholinergic mechanisms have no effect on basal prolactin, secretion but exert a weak inhibitory effect under conditions of dopamine receptor block- ade. Differences in intrinsic anticholinergic properties may account for some of the variations in po- tency of different neuroleptics in increasing circulating prolactin concentrations. Introduction In previous work we found that in patients maintained on chronic neuroleptic therapy some of the groups had higher basal prolactin concentrations if they were also receiving con- comitant anticholinergic antiparkinsonian drugs (De Rivera et al, 1976). Whereas there is evi- dence that cholinergic mechanisms modulate prolactin secretion in animals (Chen and Meites 1975; Gala et al., 1976, Subramanian and Gala, 1976; McLean and Nikitovitch-Winer, 1975), less information is available in man. Neuroleptics show considerable variation in central anticholinergic potency (Snyder et al., 1974) and also in their capacity to stimulate prolactin secretion (Langer et al., 1977). Re- cently, it has been shown that clozapine, an effective antischizophrenic agent with potent central antimuscarinic properties (Miller and Hiley, 1974), has no (Sachar et al, 1976) or 1 This work was supported by grants from the Medical Research Council (Canada). Additional sup- port was received from the G.W. Stairs Memorial Fund, McGill University and Merck Frosst Labora- tories, PQ, Canada. only weak stimulatory effects on prolactin secretion (Nair et al., 1978) in man. In order to investigate the possible role of anticholinergic mechanisms in neuroleptic-induced prolactin secretion, we have looked at the effect of benztropine, a muscarinic receptor-blocking agent, on haloperidol-induced prolactin secre- tion in normal subjects. Haloperidol was chosen because of its weak central antimuscarinic effects (Snyder et al., 1974). Subjects and Methods 10 physically healthy, nonobese male volunteers, aged 21- ST years and on no medication, served as subjects. After an overnight fast, at 7:30–8:00 a.m., a 19-gauge scalp vein needle was inserted into an arm vein and kept open with heparin saline. 60 and 90 min after insertion of the needle (–45 and –15 min), baseline samples of blood were drawn. Immediately after the sample at –15 min, subjects received either .benztropine mesylate (2 mg intramuscularly, Cogentin®) or saline intramuscularly. 15 min later, at time 0 min, the subjects were injected with haloperi- dol (1 mg intramuscularly, Haldol® or saline intra- muscularly. Additional samples of blood were taken al 30, 60, 90, 120 and 150 min. Specimens were centri- fuged and the serum stored at –20 ° C until assayed