Perinatal Dopamine-Related Drugs Demasculinize Rats

Abstract

Administration of haloperidol, a common neuroleptic, to pregnant or lactating rats impaired the masculine sex behavior of their male offspring. Prenatal haloperidol did not affect testosterone concentrations in fetuses. Maternal administration of apomorphine, a dopamine agonist, and of alpha-methyl-p-tyrosine, an inhibitor of dopamine synthesis, also demasculinized male offspring. In both experiments other behaviors and developmental milestones were unaffected. Perinatal haloperidol, apomorphine, and alpha-methyl-p-tyrosine did not lower testosterone in adulthood. These drugs may act directly on neurons that control masculine behavior without lowering testosterone prenatally or in adulthood.

Structural Effects and Neurofunctional Sequelae of Developmental Exposure to Psychotherapeutic Drugs: Experimental and Clinical Aspects

“…There is evidence that dopamine plays an important role in the regulation of sexual behavior in rats (Gessa and Tagliamonte, 1975), and dopaminergic mechanisms are thought to underlie sexual dysfunctions produced by the administration of some neuroleptics (Buffum, 1982;Segraves, 1982). In this regard, Hull et al (1984) have shown that the prolonged administration of haloperidol to pregnant rats, at a relatively high dose (2.5 mg/kg), impairs the sexual behavior of male offspring. Indeed, haloperidol-exposed animals had significantly fewer ejaculations than controls.…”

Neurohormonal functioning and sexual orientation: A theory of homosexuality–heterosexuality.

“…The list includes barbiturates, chlorimipramine, diazepam, diethylstilbesterol (DES), marijuana, pargyline, and reserpine (Domer, 1981;Hull et al, 1984;Reinisch & Sanders, 1982). In addition, progesterone and drugs similar to it-variously called progestins and progestogens (Borland'sMedico!…”

“…According to Hull et al (1984Hull et al ( , p. 1013, any drug that alters dopamine levels in the brain probably affects the sexual differentiation of the nervous system, provided that it is administered in fairly high dosages while the brain is undergoing neuro-organization (see also Dorner, Hecht, & Hinz, 1976).…”

Development of Male Sexual Function After Prenatal Modulation of Cholinergic System

“…The neurotransmitter DA plays an important role in activating the sexual behavior in male rats; DA depletion in brain structures involved in regulating the behavioral states of body facilitates reductions in sexual activity (Gladkova, 2000;Mas et al, 1987;Pfaus & Phillips, 1991). Lesioning of different dopaminergic projections induces different behavioral syndromes depending on which part of the CNS is lesioned (Carey & Schwarting, 1986;Simon et al, 1986); in particular, damage to the dopaminergic projections of limbic structures leads to impairments in male sexual function (Hull et al, 1984). The noradrenergic and serotoninergic systems of the brain are also involved in regulating hormone-dependent behavioral states, including sexual behavior (Naumenko et al, 1983;Lenahan et al, 1986;Smeets & Reiner, 1994).…”