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Biomedical subjects

A R Lumia

Publications and source records attributed to A R Lumia.

At least 19 recordsLinked to original sources

Aggression in male rats receiving anabolic androgenic steroids: effects of social and environmental provocation.

This study examined the effects of anabolic androgenic steroids (AAS) on aggression under different social and environmental conditions. Three AAS were tested in gonadally intact male rats: testosterone propionate (TP), nandrolone (ND), and stanozolol (ST). Doses of 5 mg/kg were given 5 times/week, with gonadally intact controls receiving vehicle only (propylene glycol). Animals received six weekly tests under each condition in a counterbalanced order. Results show that the three AAS differed in their ability to elicit aggression. Males receiving TP were more aggressive than controls, ND males were similar to controls, and ST males were less aggressive than controls. In the social and environmental provocation tests TP-treated males were more aggressive than other groups, but were able to discriminate between intact and castrated opponents and between their home cage and a neutral cage. In the environmental provocation test, TP males were also more aggressive against opponents when tested in the opponent's home cage. It is suggested that chronic exposure to high levels of TP does not eliminate the ability to discriminate between social or environmental cues, as might be expected if it induces a " 'roid rage." However, TP does increase the likelihood that the animal will respond with aggression/dominance in a provoking situation. All three AAS variably affected serum testosterone and LH levels, as well as testes, seminal vesicle, and prostate weights. No effect on body weight was observed.

Aggression↗

The effect of anabolic-androgenic steroids on sexual behavior and reproductive tissues in male rats.

This study assessed the effects of high doses of anabolic-androgenic steroids (AAS) and their withdrawal on male reproductive behavior and reproductive tissues during development. Prepubertal, peripubertal, and adult male Long Evans rats were divided into 4 groups: 1) Testosterone propionate for 16 weeks (TP), 2) TP for 3 weeks and withdrawn for 13 weeks (TPWL), 3) TP for 16 weeks and withdrawn for 3 weeks (TPWS), 4) propylene glycol (control vehicle) for 16 weeks (PG). As determined by sexual performance and sexual preference tests, administration of high doses of AAS to the peripubertal animals enhanced sexual performance and sexual motivation. There was no significant effect on sexual behavior of the prepubertal animals. High doses of anabolic-androgenic steroids depleted Leydig cell number in the prepubertal and adult rats, but had no effect on the Leydig cell number of the peripubertal animals. After long-term withdrawal from AAS no significant effects on sexual behavior were found. The depletion of Leydig cells that occurred in the prepubertal animals after withdrawal was reversible, while the depletion of the Leydig cells of the adult animals did not return to the control level suggesting a long lasting alteration.

Anabolic Agents↗

Effects of fluoxetine and olfactory bulbectomy on mouse circadian activity rhythms.

Olfactory bulbectomy (OBX) in SWR outbred male mice lengthened the free-running period and delayed the phase of a circadian rhythm for wheel-running activity. OBX also increased mean levels of activity. Two weeks of daily intraperitoneal injections of Fluoxetine (8 mg/kg), a serotonin re-uptake inhibitor, reversed the effects of bulbectomy on the mean level of activity and significantly shortened the free-running period of the activity rhythm. The phase of the activity rhythm was not significantly affected by the Fluoxetine treatment. These results are consistent with a hyposerotonergic mediation of the effects of OBX on circadian period and activity level.

Animals↗

Inhibition of male sex behavior by androgen receptor blockade in preoptic area or hypothalamus, but not amygdala or septum.

Inhibition of masculine copulatory behavior was previously demonstrated following systemic injections of hydroxyflutamide (OHF). In the present study, we examined the localization of the effects of this androgen receptor blocker by direct intracranial implantation of OHF into the medial preoptic area (MPOA), ventromedial nucleus of hypothalamus (VMN), medial amygdala (AME), and lateral septum (SEPT). Animals were implanted intracranially with crystalline OHF or cholesterol, and at the same time received two 10-mm testosterone-filled Silastic capsules SC. Tests for restoration of copulatory behavior were initiated 3 days later, and conducted twice weekly for 2 weeks. Implants of OHF into the MPOA were effective in preventing restoration of male sexual behavior. However, the most effective site was the VMN. Implants of OHF into the AME were only partially effective in stimulating male sexual behavior, whereas implants into the SEPT had no effect. The OHF was discontinued and 1 week later males were retested for sexual behavior. The majority of these animals ejaculated, indicating, that the effects of OHF are reversible. The result of this study demonstrate that the functional integrity of androgen receptors in some, but not all, androgen-concentrating brain loci is necessary for the expression of the complete pattern of male sexual behavior. These data lend support to the view that androgen receptor populations in specific brain loci differentially express proteins involved in mediating the masculine copulatory response.

Amygdala↗

Effects of chronically high doses of the anabolic androgenic steroid, testosterone, on intermale aggression and sexual behavior in male rats.

To determine if chronic exposure to high doses of anabolic androgenic steroids (AAS) increase aggression and sexual activity in gonadally intact rats, we administered SC injections of testosterone propionate (TP: 1 mg) or propylene glycol (PG: as a vehicle control) three times per week for 10 consecutive weeks. Weekly tests for male copulation were conducted by pairing each male with a sexually receptive female in a glass arena and recording various parameters of copulation. Chronic treatment with TP did not alter any parameter of male copulation including ejaculation and post ejaculatory interval. Sexually experienced males were tested once per week for intermale aggression in a neutral environment. For aggression tests, each experimental animal was placed into an arena with an opponent male for 15 min. The opponent, a gonadally intact male, was used only for the purpose of the aggression test. Frequencies of dominance, submissive, threat, and fight postures, as well as approaches were scored for each animal. TP-treated males did not differ in body weight from PG-treated males, suggesting that the increased aggression was not due to increased body mass. The results of this study show that chronic exposure to the anabolic androgenic steroid, testosterone, potentiates male aggressive response patterns but does not alter male sexual behavior or body weight.

Aggression↗

Olfactory bulbectomy as a model for agitated hyposerotonergic depression.

Ablation of olfactory bulbs in rats reduced male sexual behavior, and altered the distribution of wheel-running activity between the light and dark phases of a 12:12 LD photoperiod. These effects were partially reversed by the tricyclic antidepressant amitriptyline. Olfactory bulbectomy also altered serotonin metabolism (5-HIAA/5-HT ratio) in the frontal cortex, nucleus accumbens, hippocampus and corpus striatum. These observations support the hypothesis that olfactory bulbectomy in rodents serves as a model of agitated hyposerotonergic depression.

Amitriptyline↗

The effects of olfactory bulbectomy and chronic psychosocial stress on serum glucocorticoids and sexual behavior in female rats.

The effects of olfactory bulb removal (OBX) and chronic psychosocial stress on serum glucocorticoids and sexual behavior were assessed in female rats primed with a subthreshold level of estradiol (E2). Ovariectomized females underwent either OBX or sham surgery. Half of the OBX and half of the sham animals were exposed to chronic psychosocial stress (crowding, strobe light, and intermittent noise) for one-half h per day for 27 days. On day 22, three blood samples were collected from each animal for serum corticosterone analysis; 1) before, 2) during, and 3) after acute stress (one-half h restraint). On day 28, females were exposed to either 4 or 24 h of E2. On day 29, all females received 500 micrograms progesterone (P) 4 h prior to sexual behavior testing. Sexual receptivity was measured using the lordosis quotient (LQ = [number of lordotic responses/10 mounts] x 100). Sexual proceptivity (dart and ear wiggling sequences) and rejection (number of nonlordotic responses to mount attempts) were measured throughout a 10-min test period. Results showed that chronic psychosocial stress dramatically increased sexual receptivity and proceptivity while decreasing sexual rejection in female rats primed with a subthreshold level of E2. Chronic psychosocial stress also elevated serum glucocorticoids and significantly exacerbated the glucocorticoid response to acute stress. OBX, while increasing sexual receptivity and decreasing sexual rejection, had no effect on serum glucocorticoids. These findings support the hypothesis that OBX potentiates female sexual behavior directly through an increase in neural sensitivity to E2. In contrast, the enhancing effect of chronic psychosocial stress on female sexual behavior may result from alterations of the hypothalamo-pituitary-adrenal system.

Animals↗

Fluoxetine shortens circadian period for wheel running activity in mice.

Fluoxetine is a potent and specific serotonin re-uptake inhibitor and an effective antidepressant drug. Male mice were treated with either fluoxetine (8 mg/kg body weight per day) or saline. Wheel running activity was monitored for 2 weeks in a 12:12 LD cycle followed by 2 weeks in constant darkness (DD). Fluoxetine significantly shortened free-running circadian period for wheel running activity (23.93 +/- 0.08 h for fluoxetine treated mice versus 24.17 +/- 0.07 h for saline treated mice; p less than 0.03). These results are consistent with a role for serotonin in the regulation of circadian period in mice.

Animals↗

Effects of ovarian hormones on sexual receptivity, proceptivity, and motivation in olfactory bulbectomized female rats.

The purpose of the present experiment was to assess the effect of olfactory bulbectomy and ovarian hormones on female sexual motivation. Ovariectomized female rats underwent either bilateral bulbectomy or sham surgery. Females received one of four subthreshold hormone treatments: 0% estradiol (E2) plus 500 micrograms progesterone (P), 100% E2 alone, 10% E2 plus 500 micrograms P, or 100% E2 plus 500 micrograms P. Sexual motivation (as indicated by a female's preference for a sexually active male over a castrated male) and proceptivity (dart and ear wiggling sequences) were measured in a three compartment partner preference apparatus. Sexual receptivity (lordosis) was measured separately in a glass arena with a sexually active male. Results showed that olfactory bulb removal facilitates sexual receptivity and proceptivity in females exposed to 10% or 100% E2 in combination with 500 micrograms P. In contrast, sexual motivation was only demonstrated by olfactory bulbectomized females which received 100% E2 in combination with 500 micrograms P. These findings support the hypothesis that olfactory bulbectomy induces a behavioral hypersensitivity to estrogen, and suggest that sexual motivation is an estrogen-mediated response which requires a higher level of estrogen stimulation than sexual receptivity and proceptivity.

Animals↗

Olfactory bulbectomy increases basal suprachiasmatic cyclic AMP levels in male rats.

For further characterization of the olfactory bulb's role in the medication of chronobiological phenomena, we examined basal cyclic- 3',5'-adenosine monophosphate (cAMP) levels in the suprachiasmatic nuclei (SCN) and lateral hippocampus (LHIP) following bilateral olfactory bulbectomy (OBX) to assess the effects of olfactory bulb removal on the biological clock. Two groups of adult Long-Evans rats underwent OBX or sham control surgery (SHAM). Eight weeks postoperative, the animals were decapitated at the time of maximal cAMP accumulation (circadian time 9-11 h), brains were removed, frozen in liquid nitrogen, and sectioned on a cryostat. Individual brain nuclei (SCN and LHIP) were microdissected using the Palkovits punch technique and analyzed by scintillation proximity assay for cAMP. We report a 83.6% increase in basal cAMP levels in the SCN following OBX (OBX = 63.7 pmol cAMP/mg protein, SHAM = 34.7 pmol cAMP/mg protein, p less than 0.01). No significant differences in LHIP cAMP levels were found. This specific increase in SCN cAMP, at the time of maximum cAMP accumulation, may give insight into the biochemical basis for altered activity levels following OBX.

Animals↗

Olfactory bulb control of circadian activity rhythm in mice.

Ablation of mouse olfactory bulbs lengthened the circadian period of wheel-running activity by 43 min and delayed the onset of entrained activity by 108 min. A transient increase in activity during the light phase of the 12:12 h light-dark photoperiod also occurred following surgery. These disruptions suggest that olfactory systems can modulate mammalian circadian rhythms.

Animals↗

Olfactory bulb removal decreases androgen receptor binding in amygdala and hypothalamus and disrupts masculine sexual behavior.

In these experiments we examined the relationship between olfactory bulb removal, limbic system androgen receptor binding and male copulatory behavior. Sexually experienced male rats were castrated, and implanted with two 10 mm testosterone-filled silastic capsules. Animals then underwent either bilateral olfactory bulb removal (BOB) or sham surgery (Sham). Beginning 1-2 days postoperatively both BOB and Sham operates were given 4 tests for male copulation on alternate days. Less than 40% of BOB males ejaculated. In contrast, 80-100% of sham operates continued to ejaculate throughout the 4 postoperative tests. Cell nuclear androgen receptor binding was assessed in amygdala, hypothalamus, preoptic area and septum 1-2 and 8-9 days after either bulbectomy or sham surgery. We found that olfactory bulbectomy significantly reduces androgen receptor binding in amygdala and hypothalamus. The reduction in androgen receptor binding in amygdala occurs within 1-2 days following olfactory bulb removal and is correlated with the disruption of ejaculatory activity. These data suggest that the neuromodulation by olfactory bulb input to androgen-concentrating neurons in the amygdala and hypothalamus is necessary for effective copulation in male rats.

Amygdala↗

Increased estrogen receptor binding in amygdala correlates with facilitation of feminine sexual behavior induced by olfactory bulbectomy.

In this experiment we tested the hypothesis that the potentiation of feminine sexual behavior following olfactory bulb removal in female rats would be associated with increased ovarian steroid receptor binding in brain. Ovariectomized adult female rats underwent either bilateral olfactory bulb removal (BOB) or a sham operation and were exposed to 100% estradiol (E2) in silastic capsules for 4 or 6 h. Following behavior testing, either cell nuclear estrogen receptor levels were measured in amygdala, hypothalamus, preoptic area and pituitary, or cytosol progestin receptors levels were determined in cortex, preoptic area and hypothalamus. After 6 h E2 exposure, BOB females showed increasing lordosis responding with increasing progesterone (P) doses, at levels significantly higher than those of sham-operated rats. After 4 h E2 exposure bulbectomized rats showed both a facilitation of lordosis and elevated estrogen receptor levels in amygdala. Sham-operates showed neither response to the 4 h E2 stimulus. For both BOB and sham groups, progestin receptors were induced after 6 h E2 exposure, but were uninduced after 4 h E2 exposure. Additional rats were exposed to 5% E2 for 24 or 48 h, followed by P. Lordosis was potentiated in BOB rats at 24 h; sham-operates showed high levels of lordosis only after 48 h of 5% E2 exposure. Proceptivity was enhanced in BOB rats after both 24 and 48 h of 5% E2 exposure. In contrast, proceptivity was rarely observed in sham-operates, or in either group after 4 or 6 h E2 exposure. We propose that increased estrogen receptor binding in the amygdala may provide a biochemical basis for the increased estrogen sensitivity found in olfactory bulbectomized female rats.

Amygdala↗

Sympathetic control of sexual reflexes: peripheral 6-hydroxydopamine administration facilitates the onset of penile reflexes in male rats.

The latency to display penile reflexes was significantly reduced in male rats tested one day following treatment with 6-hydroxydopamine (6-OHDA; 75 mg/kg, administered via acute tail vein injection). Eight days following treatment the latency to the first reflex in 6-OHDA treated males did not differ significantly from saline treated control subjects. There were no significant differences in the mean number of erections or flips displayed by 6-OHDA subjects when compared to saline treated control subjects. On tests one day after 6-OHDA administration, treated subjects displayed significantly fewer cups than control subjects on the corresponding tests. Chemical sympathectomy was verified by extreme reduction of peripheral norepinephrine levels. Results of this study are consistant with those reported for spinally transected rats tested under similar conditions (that is, one day following spinal transection), and suggest sympathetic inhibition of the onset of penile reflexes.

Animals↗

Olfactory and vomeronasal system mediation of maternal recognition in the developing rat.

Olfactory-mediated arousal and maternal recognition were evaluated in neonatal rat pups. Non-nutritionally deprived pups which underwent bilateral olfactory bulbectomies on day 5, failed to distinguish between the ventral and dorsal surfaces of a nursing rat and a heating pad. They showed virtually no arousal response to any of these surfaces. In contrast, pups with unilateral bulbectomies, and sham controls, graded their arousal response, and were maximally aroused by the mother's ventral surface. Following 24 h of maternal deprivation, bilaterally bulbectomized pups displayed a modest arousal response, directed primarily towards the dorsal surface. Pups with complete vomeronasal nerve sections displayed maximal arousal responses toward the dorsal surface. However, they were far more aroused than the bilaterally bulbectomized pups. Rat pups with incomplete vomeronasal lesions graded their response like controls, with maximal responsiveness directed toward the ventral surface. Shaving the dorsal surface markedly diminished the arousal response of bilaterally bulbectomized pups, but had only modest effects on sham and unilaterally bulbectomized controls. Thus, lesions that destroyed both the main and accessory's olfactory bulb systems severely impaired the pups' ability to effectively recognize a lactating female and markedly diminished maternally-induced arousal. Selective damage to the vomeronasal-accessory olfactory system appeared to disrupt discriminative capacity, but had little effect on the magnitude of the arousal response.

Animals↗

Induction of female and male mating patterns in female rats by gonadal steroids: effects of neonatal or adult olfactory bulbectomy.

Hormonally mediated sexual response patterns were evaluated in female rats receiving olfactory bulb ablations neonatally (Day 2) or in adulthood. In a test of females' reactivity to a caged male in an open field, estrogen and progesterone treatments increased the number of squares entered and the number of cage contacts, but olfactory bulb removal had no effect on these measures. During mating tests, the feminine sexual behavior of females bulbectomized on Day 2 was similar to that of control-operated females, whereas females bulbectomized as adults displayed enhanced levels of lordosis, darting, and ear wiggling. Lordosis varied with estrogen dose, whereas darting was progesterone-dependent. In tests of masculine copulatory behavior, the proportion of bulbectomized females (Day 2 and adult) that mounted was significantly lower than that of control-operated females. The effects of olfactory bulb removal, which vary with the age at ablation and the behavioral system investigated, are not mediated by a single neuroendocrine system and cannot be interpreted in terms of a unitary "arousal' construct.

Animals↗