Blockade of androgen receptor in the medial amygdala inhibits noncontact erections in male rats
Research highlights
► Flutamide in the medial amygdala inhibit noncontact erections. ► ATD in the medial amygdala do not diminish noncontact erections. ► The medial amygdala is sensitive to relatively fast changes in androgen receptors activation.
Introduction
One of the most useful parameters describing sexual arousal is the occurrence of penis erection. In male rats exposed to inaccessible estrous females the presence of penile erections can be useful model to investigate the neuronal structures involved in the regulation of sexual arousal [40]. These noncontact erections (NCEs) are analogous to human "psychogenic" erections [37] and are presumed to reflect sexual arousal [39]. Sachs [39] analyzed mechanisms involved in the regulation of erections and concluded that neuronal structures and hormonal profile depend on the context in which erection occurs.
NCEs disappear within three days after castration and are restored within a few days by subcutaneous implants of testosterone (T) or dihydrotestosterone (DHT), but not by estradiol (E) [5], [25]. NCEs were not significantly affected in aromatase knockout mice, suggesting that the role of estrogens is small, if at all, in this phenomenon [27]. This profile of hormone sensitivity is similar to that of touch-based erections in rats, which were maintained or restored by T and DHT, but not by E, whereas male rat copulatory behavior (mounting and intromissions) responds to systemic T and E, but not to DHT [17], [30]. Intromissions (erections during copulation) were visible much longer than NCEs—they usually could be detected at least one week after castration. Touch-based erections disappeared earlier in castrated rats and were restored quicker than erections during copulation [17]. The first effect of hormonal therapy on touch-based erection occurred after 24 hours (with a maximum after 48 hours) at the time when intromissions were not visible [10]. After spinal transection, touch-based erection reappeared even faster—i.e. within hours [13]. It hardly seems possible that morphological changes in the spinal neuronal structures would develop during this time. It was recently found that loss of penile reflexes did not correspond with the time course of morphological changes either in the spinal nucleus of the bulbocavernosus innervating striated muscles of the penis (first significant effect on day 28) or striated muscles of the penis itself (bulbocavernosus and levator ani, first effect on day 14) after castration [12].
The amygdala integrates sensory and hormonal inputs involved in the regulation of sexual behavior [7], [17], [26], [49]. Volatile odors from the female are necessary and sufficient to evoke NCEs in male rats [8], [38]. Informations about such odors are transmitted via the main olfactory system [21]. Lesions of the medial amygdala (MeA)—especially in the postero-dorsal part (MeApd)—eliminate or severely disrupt NCEs, and to a lesser extent, disrupt copulation [19], [20]. In contrast, medial preoptic area (MPOA) lesions eliminate copulation without significantly disrupting NCEs [22]. The MeApd of rats is sexually dimorphic [14], and the size depends on the activation of androgen [6]. However, the dorsal region of the MeA of male rats is rich not only in androgen receptors, but also estrogen receptors [11], [44], and the postcastration atrophy of neurons in MeApd is reversible by systemic DHT or E [5]. The androgens in the medial amygdala are ineffective in the restoration of copulation in long-term castrated males [48] unless they receive subthreshold levels of systemic estradiol [1]. Blocking of androgen receptors by hydroxyflutamide did not significantly disturb the restoration of copulation in castrated males during hormonal testosterone therapy [29]. Estradiol in the medial amygdala facilitates some elements of copulatory behavior—mounting and intromission frequency but not ejaculation [16].
The androgen implants into medial amygdala briefly maintain noncontact erections after castration. About half of the males implanted with T or DHT into MeA at the time of castration showed NCEs one week later. Moreover, latency to first NCE was reversibly correlated with androgen concentration in the postero-dorsal part of MeA. The role of estrogens in MeA was not clear, as NCEs were detected two weeks after E implantation. In this experiment androgens as well as estradiol had marginal effect on copulation—increased number of males displaying mounting two weeks after castration [3].
Because NCEs disappear within three days after castration [25], it suggests a relatively fast regulation of such erections by androgens when compared to erections during copulation. It should be noted that the term “fast” does not mean the same as “rapid” because “rapid” is related to the process that does not require protein synthesis. Androgen administration can be executed by influences on penis or penis innervations and/or brain structure such as the MeA. Also because many aspects of copulatory behavior correlate with aromatase of testosterone activity [17], we decided to investigate the effects of androgen receptors and testosterone aromatization block in the MeA on NCEs simultaneously in the experiment described in this article.
The aim of our study was to establish whether the relatively fast effects of androgen receptors activation on noncontact erections can be mediated by the medial amygdala. We analyzed noncontact erections in intact male rats within the first days of drug administration, after the blocking of androgen receptors in the medial amygdala. Additionally, we blocked aromatization of testosterone to investigate the effect of lower levels of estradiol in the MeA on NCEs phenomenon.
Section snippets
Methods
In general, the scheme of experiments was based on methods described in our previous experiments [3].
Histology
Only animals with cannulae successfully implanted into at least one side of the MeA (Fig. 1) were analyzed statistically. The mean sum of both cannulae tips (3 pdMeA, 2 border pd-adMeA, 1 adMeA, 0 out of MeA) in F group was 3.44 (SE = 0.58). The mean sum of cannulae tips in ATD group was 4.25 (SE = 0.62). The cannulae of 7 males were localized outside of the MeA mostly to lateral ventricle. Twelve males from control (C), nine from F and eight from ATD treated groups were qualified for statistical
Discussion
The results of this study suggest that in the MeA (i) androgen receptors play a significant role in the regulation of NCEs; (ii) blocking the androgen receptors displays fast inhibition of NCEs; (iii) blocking P-450 testosterone aromatase activity does not diminish NCEs.
Acknowledgments
This work was supported by a grant from the Medical University of Warsaw (1MA/W1/2004-6). The protocols were approved by The Animal Care and Use Committee of The Medical University of Warsaw (2003). We thank Ewa Szczepańska-Sadowska and Maciej Śmietanowski for many useful suggestions and Robert Crayton and Peter James for language correction.
References (50)
- et al.
Implantation of dihydrotestosterone propionate into the lateral septum or medial amygdala facilitates copulation in castrated male rats given estradiol systemically
Horm Behav
(1982) - et al.
Androgen implants in medial amygdala briefly maintain noncontact erection in castrated male rats
Horm Behav
(2002) - et al.
Rapid action on neuroplasticity precedes behavioral activation by testosterone
Horm Behav
(2008) - et al.
Both estrogen receptors and androgen receptors contribute to testosterone-induced changes in the morphology of medial amygdala and sexual arousal in male rats
Horm Behav
(2003) - et al.
Deafferentation of the olfactory bulbs of male rats reduces erection to remote cues from female
Physiol Behav
(1997) - et al.
Dynamic of male sexual arousal: distinct components of brain activation revealed by fMRI
Neuroimage
(2005) - et al.
Hormonal regulation of penile erection in castrated male rats
Physiol Behav
(1980) - et al.
Time course of adult castration-induced changes in soma size of motoneurons in the rat spinal nucleus of the bulbocavernosus
Neurosci Lett
(2009) - et al.
Differences in responsiveness to testosterone of penile reflexes and copulatory behavior of male rats
Horm Behav
(1983) - et al.
Sex differences in subregions of medial nucleus of amygdala and the bed nucleus of stria terminalis of the rat
Brain Res
(1992)
Androgen receptor blockade in the posterodorsal medial amygdala impairs sexual odor preference in male rats
Horm Behav
Estradiol in the male rat amygdala facilitates mounting but not ejaculation
Physiol Behav
Male sexual behavior
Effects of ATD on male sexual behavior and androgen receptor binding: a reexamination of the aromatization hypothesis
Horm Behav
Disparate effects of small medial amygdala lesions on copulation, noncontact erection, and partner preference
Physiol Behav
Importance of the medial amygdala in rat penile erection evoked by remote stimuli from estrous females
Behav Brain Res
Rapid steroid influences on visually guided sexual behavior in male goldfish
Horm Behav
Olfactory bulb removal decreases androgen receptor binding in amygdala and hypothalamus and disrupt masculine sexual behavior
Brain Res
Regulation of noncontact erection in rats by gonadal steroids
Horm Behav
Lesions that functionally disconnect the anterior and posterodorsal sub-regions of the medial amygdala eliminate opposite-sex odour preference in male Syrian hamsters (Mesocricetus auratus)
Neuroscience
Neurological effects of aromatase deficiency in the mouse
J Steroid Biochem Mol Biol
Inhibition of male sexual behavior by intracranial implants of the protein synthesis inhibitor anisomycin into the medial preoptic area of the rat
Horm Behav
Inhibition of male sex behavior by androgen receptor blockade in preoptic area or hypothalamus, but not amygdala or septum
Physiol Behav
Differential maintenance of penile responses and copulatory behavior by gonadal hormones in castrated male rats
Horm Behav
Anisomycin does not disrupt the activation of penile reflexes by testosterone in rats
Physiol Behav
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