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Hormones of the hypothalamo-pituitary-gonadal axis in drug discrimination learning.

More than 30 years ago, T-maze studies with progesterone indicated that sex hormones have the potential to act as a discriminative stimulus in rats. Despite these early positive findings, the interest in discriminative stimulus properties of sex hormones remained low; few studies were dedicated to the investigation of discriminative stimulus properties of hypothalamo-pituitary-gonadal axis hormones (i.e., LHRH, LH/FSH, sex steroids). Nevertheless, the few studies that were published showed some interesting, and often sex-dependent results. Applying various methodologies (T-, or Y-maze, two-lever drug discrimination, taste aversion procedures), it was found that not only progesterone but also the two other principal sex steroids estradiol and testosterone can serve as discriminative stimuli in rodents. In addition to these gonadal hormones, the hypothalamic peptide LHRH (having a key role in the neuroendocrine regulation of steroid release from the gonads) appears to generate discriminative stimulus properties. Interestingly, recent (but preliminary) studies in postmenopausal women suggest that estradiol (and possibly progesterone) may also function as a discriminative stimulus in human subjects.