3 alpha-hydroxy-5 alpha-pregnan-20-one in the midbrain ventral tegmental area mediates social, sexual, and affective behaviors

Progestins mediate the onset and duration of lordosis, the mating posture of female rodents, through actions in the hypothalamus and ventral tegmental area. In the hypothalamus, progesterone has traditional, genomic actions via intracellular progestin receptors. In the ventral tegmental area, 3 alpha-hydroxy-5 alpha-pregnan-20-one has non-genomic actions independent of progestin receptors to facilitate lordosis that involve GABA(A)/benzodiazepine receptors, NMDA type glutamate receptors, and/or dopamine receptors. 3 alpha-Hydroxy-5 alpha-pregnan-20-one levels also change with behavioral and/or environmental stimuli and may have a role in other reproductively-relevant behaviors, such as affiliation, exploration, and anxiety (socio-sexual behaviors). Data are reviewed that support the notion that: 1) effects of 3 alpha-hydroxy-5 alpha-pregnan-20-one in the midbrain ventral tegmental area facilitate lordosis and other reproductively-relevant behaviors. 2) 3 alpha-Hydroxy-5 alpha-pregnan-20-one, formed in the ventral tegmental area from metabolism of progestins, produced peripherally by endocrine glands, or centrally from biosynthesis in glial cells mediates socio-sexual behaviors. 3) 3 alpha-Hydroxy-5 alpha-pregnan-20-one's actions at GABAA/benzodiazepine receptors, NMDA type glutamate receptors, and dopamine receptors in the ventral tegmental area are important for lordosis; however, effects at these substrates on socio-sexual behaviors have not been elucidated. Given 3 alpha-hydroxy-5 alpha-pregnan-20-one's involvement in stress responses, its putative role as a homeostatic regulator and in the pathophysiology and treatment of neuropsychiatric disorders is discussed. (C) 2005 Published by Elsevier Ltd on behalf of IBRO.