Post-weaning social isolation of male rats reduces the volume of the medial amygdala and leads to deficits in adult sexual behavior

Abstract

At 21 days of age, gonadally intact male Long Evans rats were weaned and placed into standard laboratory conditions (three per cage) or housed singly. They were tested for noncontact erections and sexual performance at 90 and 220 days of age. Rats raised in isolation displayed significantly fewer noncontact erections in response to sensory cues from an estrous female and fewer intromissions when allowed to mate with a female than did males raised in groups. The volume of the posterodorsal component of the medial amygdala (MePD) and the size of neurons within the MePD were significantly smaller in the isolated males than in socially housed males. Similarly, neurons in the sexually dimorphic nucleus of the preoptic area (SDN-POA) were smaller in isolate animals than in controls. As both MePD volume and SDN-POA soma size are responsive to sex steroids, these differences could result if the isolates experienced lower testosterone levels. Finally, the volume of the overall medial amygdala (MeA) correlated significantly with the number of noncontact erections, a relationship that was not explained by housing condition. These findings highlight the role of social experience as a factor in the sexual differentiation of the brain and suggest a positive relationship between the volume of a brain structure and the display of sexual behaviors.

Introduction

The orthodox model of brain sexual differentiation views gonadal steroids as the primary agent in effecting change in the nervous system [4]. This view is being enriched, however, with evidence of reciprocity among the effects of gonadal steroids, behavioral experience and the neural plasticity and/or neurogenesis that results from such experiences [3], [22], [38]. The possibility that behavioral experience may have an effect on sexually dimorphic brain regions is particularly salient in the case of juvenile rough and tumble play, which occurs with greater frequency among male rats than females [35]. Neonatal androgen masculinizes the play of females, and this effect appears to be mediated by the medial amygdala (MeA), since androgen implants directed at this structure have the same effect as systemic treatments [36]. The MeA also appears to be involved in several sexually dimorphic social behaviors in the adult animal, including chemosensory investigation of females [9], [50], conditioned avoidance of a dominant conspecific [28] and intermale aggression [48]. The function of the MeA in social behaviors throughout life raises the possibility that juvenile experiences such as play may be necessary to prepare MeA circuits involved in adult behaviors.

The MeA receives sensory information from the accessory olfactory bulb [26], [44], the cerebral cortex and hippocampus [34], and projects to motor and endocrine centers in the basal telencephalon, hypothalamus and midbrain [7]. One behavior recently associated with the MeA is noncontact erections (NCE). These may provide an index of ‘psychogenic’ sexual arousal since NCE are displayed when the male rat is in the presence of an estrous female but is prevented from copulating with her [42]. Lesion studies [25], as well as, castration and hormone replacement experiments [32] suggest that the MeA is necessary for the production of NCE in rats and that the primary hormone activating the MeA is dihydrotestosterone.

As might be expected if the MeA contributes to male sexual arousal, it has a greater volume in male rats than in females. The posterodorsal nucleus of the MeA (MePD) has been consistently identified as the most sexually dimorphic subnucleus within the MeA [16], [23]. Recently, we found that the adult volume of the MePD is sensitive to circulating androgens. Castration of adult males led to female-like MePD volumes after 30 days, whereas castrating females and treating them with testosterone led to MePD volumes comparable to those of the control males [8]. Other MeA sub-nuclei display little or no changes with adult hormone manipulations (unpublished observations). Studies in various rodents have shown that dendritic branching and the expression of neuropeptides such as substance P, cholescystokinin and vasopressin in the MeA are all sensitive to circulating sex steroids [10], [15], [30], [31], [41], [45].

Social isolation during development affects sociosexual behavior in both rats and nonhuman primates [13], [17], [33]. Socially isolated rats display copulatory deficits [1], abnormal gonadal steroid synthesis [12], [29] and higher than normal glucocorticoid secretion [47]. Although these studies indicate that post-weaning social isolation has negative consequences on the adult sexual behavior, there has been relatively little investigation of the effects of isolation on the morphology of limbic structures that are involved in sexual arousal and copulation.

We sought to examine the effect of social isolation on the volume of the MeA, the volume of each of its four subnuclei and the soma size of neurons in these subnuclei. We asked whether animals deprived of the opportunity to interact with their peers would, in adulthood, have a smaller MeA and display deficits in sexual behavior such as NCE. We also examined the size of neurons in the SDN-POA, a component of the medial preoptic area that receives efferents from the MeA [7] and is known to be responsive to changes in adult androgen [2].