Maternal gestational androgens are associated with decreased juvenile play in white-faced marmosets (Callithrix geoffroyi).

Exposure to androgens during prenatal development shapes both physiological and behavioral developmental trajectories. Notably, in rhesus macaques, prenatal androgen exposure has been shown to increase rough-and-tumble play, a prominent behavioral feature in males during the juvenile period in primates. While macaques are an Old World, polygamous species with marked sexually dimorphic behavior, New World callitrichine primates (marmosets and tamarins) live in cooperative breeding groups and are considered to be socially monogamous and exhibit minimal sexual dimorphism in social play, which suggests that androgen may affect this species in different ways compared to macaques. In addition, we previously described considerable variation in maternal androgen production during gestation in marmosets. Here we tested the association between this variation and variation in offspring rough-and-tumble play patterns in both males and females. We measured testosterone and androstenedione levels in urine samples collected from pregnant marmoset mothers and then observed their offspring's play behavior as juveniles (5-10 months of age). In contrast to findings in rhesus macaques, hierarchical regression analyses showed that higher gestational testosterone levels, primarily in the second semester, were associated with decreased rough-and-tumble play in juveniles, and this relationship appears to be driven more so by males than females. We found no reliable associations between gestational androstenedione and juvenile play behavior. Our findings provide evidence to suggest that normative variation in levels of maternal androgen during gestation may influence developmental behavioral trajectories in marmosets in a way that contradicts previous findings in Old World primates.

Fetal testosterone surge: specific modulations induced in male rats by maternal stress and/or alcohol consumption.

Plasma testosterone (T) was measured in control male and female rats on gestational days 16, 17, 18, 19, and 20 and on days 17-20 in males from dams who were fed ethanol and/or were stressed during pregnancy. Circulating T in control males showed an earlier rise, yielding a longer period of prenatal T elevation, than was reported previously (Endocrinology 106 (1980)306). Compared to control males, exposure to alcohol-alone augmented T on days 18 and 19, stress-alone attenuated prenatal T, and the combination of stress and alcohol completely blocked the normal rise in T between days 17 and 18. When these prenatal alterations in T are viewed along with effects these same treatments have on the postparturient T surge (Horm. Behav. 41 (2002) 229), a possible explanatory mechanism emerges for the uniquely different behavioral patterns of sexual behavior differentiation induced in males by prenatal exposure to alcohol, stress, or both factors. Whereas the potential for feminine behavior is retained to the extent that either the prenatal or the neonatal T surge is attenuated, the male potential is more sensitive to reductions in the fetal surge and is maximally disrupted if both the prenatal and the postparturitional T surges are suppressed.

Fluoxetine differentially suppresses sucrose solution consumption in free-fed and food-deprived rats--reversal by amantadine.

BACKGROUND: Clinical use of fluoxetine and similar medications is often associated with appetite suppression and weight loss that may warrant drug discontinuation. It is unclear, however, if fluoxetine-induced consummatory suppression may be influenced by factors such as dietary status and if appetite suppressant effects of fluoxetine may be pharmacologically attenuated. MATERIAL/METHODS: Fluoxetine (0.5-10 mg/kg, i.p.) was administered to free-fed and 24 hr food-deprived adult male rats either 30 min or 4 hr prior to presentation of a sucrose solution (10% v/v). Further, amantadine (5-10 mg/kg, i.p.) and fluoxetine (5 mg/kg) were both administered either 30 min or 4 hr prior to sucrose solution presentation and intake of the solution was assessed after 2 hours of exposure. RESULTS: Fluoxetine (2-10 mg/kg) administration significantly reduced sucrose solution intake in both free-fed and food-deprived rats. However, a brief treatment-test interval (30 min) resulted in a greater suppression of intake and food-deprived rats were more resistant to the suppressant effects of fluoxetine than were sated rats. Finally, the suppressant effect of fluoxetine were reversed by acute administration of amantadine (8 mg/kg) prior to sucrose solution presentation, a dose producing no inherent stimulation of consumption. CONCLUSIONS: Acute fluoxetine administration produces a reduction in palatable substance intake that is decreased in potency with a longer treatment-test interval, an effect likely not related to pharmacokinetic considerations. Further, fluoxetine-induced consummatory suppression is reduced by prior food-deprivation. Evidence that the dopamine agonist amantadine reversed fluoxetine-induced consummatory suppression suggests a role for dopaminergic antagonism in the appetite suppressant effects of fluoxetine.

Age at onset of major depressive disorder predicts reductions in NK cell number and activity.

BACKGROUND: Major depressive disorder (MDD) has been associated with altered immunologic parameters including reductions in natural killer cell activity (NKCA). It remains largely unknown, however, whether alterations in immune function characterize homogeneous sub-groups of MDD. The present study addressed the question of whether age at onset of index episode and/or duration of the present episode of MDD predicted alterations in NKCA and NK cell number. METHODS: Participants met DSM-IV criteria for MDD. Age at onset of MDD, duration of the present episode, demographics, and comorbidity were obtained by SCID for all subjects (n = 36). Severity and symptom pattern of MDD was assessed by the Hamilton Depression Rating Scale. NKCA was measured using a standard chromium-release cytotoxicity assay and NK number assessed by flow cytometry. RESULTS: Age at onset of MDD significantly predicted variance in NK cell number and NKCA. Consistent with previous studies, sleep disturbance and psychomotor retardation possessed significant explanatory power for variance in NK cell number and NKCA, respectively. LIMITATIONS: Measures of age at onset of MDD and duration of the present episode were obtained by self-report and thus recall bias may attenuate the reliability of the present findings. The present study design also precludes conclusions regarding the temporal association between alterations in NK cells and MDD. CONCLUSIONS: We propose that immunologic alterations, characterized by a suppression of NKCA and NK cell number concomitant with proinflammatory processes, may constitute an immunologic phenotype unique to early-age-onset depression and may be salient factors in the pathogenesis of depression.

Hormonal mechanisms underlying aberrant sexual differentiation in male rats prenatally exposed to alcohol, stress, or both.

The male offspring of rats exposed to restraint stress, alcohol, or both during late pregnancy show normally masculinized genitalia; however, sexual differentiation of behavior is dissociated from the external morphology. In contrast to controls, males exposed prenatally to stress, alcohol, or a combination of these factors exhibited the female lordotic pattern. Thus, all 3 prenatal treatments led to incomplete behavioral defeminization. Behavioral masculinization was not altered by fetal alcohol exposure alone, but a significant number of males that experienced prenatal stress alone failed to copulate. A more severe disruption of behavioral masculinization occurred when stress and alcohol were combined. Very few males exposed to the combination treatment mated with females. This study attempted to relate the effects of these treatments on sexual behavior to the postparturitional surge in plasma testosterone (T) that is known to influence the process of sexual differentiation. Prenatally stressed males, like control males showed a large, brief surge in plasma T that peaked 1 hr after delivery. Altered defeminization and masculinization were seen in prenatally stressed males, despite a normal postparturitional T surge. Fetal alcohol exposure, with or without concomitant stress, depressed T to the same extent right after birth and led to a similarly blunted T surge 1 hr later. Thus, equal disruption of the neonatal T pattern occurred in alcohol-alone males, who showed normal male copulatory behavior, and in alcohol-plus-stress males, whose behavior was severely attenuated. The results suggest that consideration of abnormal exposure to T during prenatal ontogeny may be required to understand the atypical sexual behaviors associated with these treatments.

Postparturitional testosterone surge in male offspring of rats stressed and/or fed ethanol during late pregnancy.

Male offspring of rats exposed to restraint stress and/or alcohol during late pregnancy show aberrant patterns of sexual behavior masculinization and defeminization that vary as a function of treatment. The impact of these treatments on the postparturitional testosterone (T) surge that contributes to sexual behavior differentiation was investigated. Plasma T was measured using radioimmunoassay in individual males sampled on day 21 of gestation within 10 min of cesarean delivery or 1, 2, or 4 h thereafter. Neonatal T in the group exposed only to stress did not differ from that in the control group. T was lower than control levels at birth in both alcohol groups. The magnitude of the T surge that occurred during the first hour of birth in the control group was diminished by 50% in both alcohol groups, whose T pattern was very similar. There was no common alteration in postparturitional T associated with the increased lordotic behavior potential that males in all three treatment groups typically share, nor were there idiosyncratic endocrine abnormalities linked to the very different male copulatory pattern each exhibits. Exposure to an abnormal T milieu during fetal as well as neonatal ontogeny may underlie the etiology of the different sexual behavior patterns exhibited by males exposed to stress and/or alcohol. Possible unique effects each treatment exerts on perinatal plasma T and it's aromatization to estradiol in hypothalamic targets are discussed.

Urinary and plasma gonadotropin concentrations in golden lion tamarins (Leontopithecus r. rosalia).

This paper describes the development and validation of a plasma and urinary gonadotropin immunoassay for golden lion tamarins (Leontopithecus rosalia), an endangered New World callitrichid primate. The assay is derived from a macaque chorionic gonadotropin assay and was validated for both plasma and urine samples in L. rosalia. Levels of immunoreactive LH/CG in lion tamarin urine were highly correlated (r = + 0.98) with gonadotropin bioactivity. Immunoreactive LH/CG levels were examined in two contexts: in the urine of adult females and in the plasma of adult males after administration of estrogen. Peaks of gonadotropin excretion were detected in samples collected from nonpregnant adult females. The peaks occurred immediately prior to cyclic elevations in urinary estrogen excretion. Plasma LH/CG concentration in males measured 24 and 48 hours after a single 50 µg injection of estradiol benzoate were significantly lower than levels at these time points measured after control treatment. Together, the results of this study point to the utility of the gonadotropin assay for monitoring reproductive function in both female and male lion tamarins.