Sex-related differences in the analgesic response to the rat tail immersion test.

The analgesic response was evaluated by the tail immersion test in adult male (N = 30), female (N = 21) and androgenized female Wistar rats (N = 15). The reaction time for tail withdrawal from the hot water bath was faster for male than for female rats (3.48 +/- 0.12 vs 6.46 +/- 0.42 s). The reaction time of androgenized female rats was similar to that of male rats (3.08 +/- 0.16 s). Blockade of opiate receptors with naloxone (2 mg/kg, ip) decreased the sensitivity to the noxious stimuli in males (4.08 +/- 0.10 s) and in androgenized females (3.69 +/- 0.19 s) but increased it in female rats (5.01 +/- 0.41 s). These data show sex-related differences in the analgesic response evaluated by the tail immersion test and indicate that administration of androgens to newborn female rats affects their pain sensitivity.

Sex-related differences in the analgesic response to the rat tail immersion test

The analgesic response was evaluated by the tail immersion test in adult male (N = 30), female (N = 21) and androgenized female Wistar rats (N = 15). The reaction time for tail withdrawal from the hot water bath was faster for male than for female rats (3.48 +/- 0.12 vs 6.46 +/- 0.42 s). The reaction time of androgenized female rats was similar to that of male rats (3.08 +/- 0.16 s). Blockade of opiate receptors with naloxone (2 mg/kg, ip) decreased the sensitivity to the noxious stimuli in males (4.08 +/- 0.10 s) and in androgenized females (3.69 +/- 0.19 s) but increased it in female rats (5.01 +/- 0.41 s). These data show sex-related differences in the analgesic response evaluated by the tail immersion test and indicate that administration of androgens to newborn female rats affects their pain sensitivity.

Sex-related differences in cardiovascular responses to common carotid occlusion in conscious rats.

Mean arterial pressure and heart rate were determined in conscious, unrestrained groups of 10 male, female and androgenized female Wistar rats 20 s (early pressor response) and 1 min (late sustained response) after bilateral carotid artery occlusion. The early pressor response, which is of carotid reflex origin, was 40% greater in female than in male rats (45 +/- 2 vs 63 +/- 3 mmHg, respectively). The late sustained response, which is of central origin (probably ischemic), did not differ between male and female rats (32 +/- 2 vs 37 +/- 4 mmHg, respectively). The magnitude of the early pressor response of androgenized female rats (50 +/- 2 mmHg) was similar to that of male rats (45 +/- 2 mmHg) but the late sustained response was 19% smaller (26 +/- 2 mmHg). Common carotid occlusion caused increases in heart rate which were greater in female (51 +/- 9 and 34 +/- 9 beats/min in the early pressor response and late sustained response, respectively) than in male rats (31 +/- 5 and 8 +/- 4 beats/min, respectively). In androgenized female rats, heart rate decreased during common carotid occlusion (34 +/- 7 and 35 +/- 8 beats/min after 20s and 1 min, respectively). These data provide evidence that there are substantial sex-related differences in the cardiovascular responses to common carotid occlusion in conscious rats and indicate that administration of androgens to newborn female rats affects the baroreceptor reflex control of their arterial pressure.

Sex-related differences in cardiovascular responses to common carotid occlusion in conscious rats

Mean arterial pressure and heart rate were determined in conscious, unrestrained groups of 10 male, female and androgenized female Wistar rats 20 s (early pressor response) and 1 min (late sustained response) after bilateral carotid artery occlusion. The early pressor response, which is carotid reflex origin, was 40% greater in female than in male rats (45 ñ 2 vs 63 ñ 3 mmHg, respectively). The late sustained response, which is of central origin (probably ischemic), did not differ between male and female rats (32 ñ 2 vs 37 ñ 4 mmHg, respectively). The magnitude of the early pressor response of androgenized female rats (50 ñ 2 mmHg) was similar to that of male rats (45 ñ 2 mmHg) but the late sustained response was 19% smaller (26 ñ 2 mmHg). Common carotid occlusion caused increases in haert rate which were greater in female (51 ñ 9 and 34 ñ 9 beats/min in the early pressor response and late sustained response respectively) than in male rats (31 ñ 5 and 8 ñ 4 beats/min, respectively). In androgenized female rats, heart rate decreased during common carotid occlusion (34 ñ 7 and 35 ñ 8 beats/min after 20 s and 1 min, respectively). These data provide evidence that there are substantial sex-related differences in the cardiovascular responses to common carotid occlusion in conscoious rats and indicate that administration of androgens to newborn female rats affects the baroreceptor reflex control of their arterial pressure

Effect of testosterone on the pressor response to common carotid occlusion in gonadectomized conscious male rats with lesion of the median eminence.

The influence of testosterone on the development of the pressor response to common carotid occlusion was investigated in control and median eminence-lesioned male rats. In control rats (N = 9), gonadectomy performed 21 days before the experiments reduced by 22% (from 51 +/- 2 to 40 +/- 2 mmHg) and treatment with testosterone (300 micrograms for 4 days before the measurements) increased the initial peak pressor response (from 51 +/- 2 to 57 +/- 2 mmHg) which depends on carotid innervation. The maintained response which is of central origin (probably ischemic) was less affected. In nongonadectomized rats (N = 6), lesions of median eminence (6 days) decreased the initial peak by 19% (from 52 +/- 2 to 42 +/- 3 mmHg) and the maintained response by 56% (from 32 +/- 2 to 14 +/- 1 mmHg). Sham-operated rats served as controls. In gonadectomized animals (N = 6) the lesion reduced only the maintained response (from 23 +/- 2 to 11 +/- 1 mmHg). Testosterone supplementation restored the maintained response but did not alter the initial peak. These results indicate that the pressor response to common carotid occlusion in male rats is modulated by testosterone and that the depression in the maintained response caused by median eminence lesion can be reversed by steroid supplementation.

Participation of opioid receptors in the modulation of the analgesic response by adrenal and gonadal glands.

The involvement of opioid receptors in the analgesic response was evaluated by the tail-immersion test in simultaneously adrenalectomized and ovariectomized female Wistar rats (210-250 g). The reaction time (mean +/- SEM) for tail withdrawal from hot water decreased significantly 2 weeks after surgery (3.52 +/- 0.20 s) when compared to intact animals (6.09 +/- 0.23 s). Hormonal replacement with dexamethasone (50 micrograms/day) did not affect reaction time (3.38 +/- 0.19 s). However, this response was restored by combined adrenal and gonadal steroid substitution (estradiol 5 micrograms/day and progesterone 1.5 micrograms 6 h before the tests) therapy (5.11 +/- 0.45 s in animals treated with dexamethasone plus estradiol and 5.04 +/- 0.43 s in animals treated with dexamethasone plus estradiol plus progesterone). Naloxone (2 mg/kg) decreased the reaction time of animals treated with adrenal and gonadal steroids (5.11 +/- 0.45 vs 4.15 +/- 0.44 s and 5.04 +/- 0.43 vs 3.87 +/- 0.28 s, respectively, before and after naloxone) but failed to decrease it in rats treated with dexamethasone only (3.88 +/- 0.18 vs 4.34 +/- 0.25 s, before and after naloxone). These observations indicate that gonadal steroids are the most important steroid factors involved in the reaction time to tail immersion in hot water and confirm other reports that the opioid pathways modulating the neuronal circuitry require the presence of these hormones.

The effect of tubero-infundibular dopaminergic neurons on prolactin and alpha-melanocyte stimulating hormone release.

The effect of tubero-infundibular dopaminergic neurons (TIDA) on the release of prolactin (PRL) and alpha-melanocyte stimulating hormone (alpha-MSH) was studied in median eminence-lesioned (MEL) male rats (N = 6-28). Plasma PRL and alpha-MSH levels were significantly elevated 2 (86.1 +/- 19.8 and 505.1 +/- 19.1 ng/ml), 4 (278.7 +/- 15.5 and 487.4 +/- 125.1 ng/ml), 7 (116.2 +/- 16.2 and 495.8 +/- 62.6 ng/ml) and 14 (247.3 +/- 26.1 and 448.4 +/- 63.8 ng/ml) days after MEL when compared to sham-operated control animals (55.5 +/- 13.4 and 56.2 +/- 6.1 ng/ml, respectively). MEL altered plasma PRL and alpha-MSH levels in a differential manner, with a 1.5- to 5.0-fold increase in PRL and an 8.0- to 9.0-fold increase in alpha-MSH. The increase of alpha-MSH levels occurred abruptly and remained constant from days 2 to 14. These observations indicate that TIDA plays an important role in the pituitary release of PRL and alpha-MSH and provide evidence that the release of the two hormones occurs in a differential manner.

Participation of opioid receptors in the modulation of the analgesic response by adrenal and gonadal glands

The invovlement of opiodi receptors in the analgesic response was evaluated by the tail-immersion test in simultaneously adrenalectomized and ovariectomized female Wistar rats (210-250g). The reaction time (mean ñ SEM) for tail withdrawal from hot water decreased significantly 2 weeks after surgery (3.52 ñ 0.20 s) when compared to intact animals (6.09 ñ 0.23 s). Hormonal replacement with dexamethasone (50*/day) did not affect reaction time (3.38 ñ 0.19 s). However, this response was restored by combined adrenal and gonadal steroid substitution (estradiol 5*g/day and progesterone 1.5*g 6h before the test) therapy (5.11 ñ 0.45 s) in animal treated with dexamethasone plus estradiol and 5.04 ñ 0.43 s in animals treated with dexamethasone plus estradiol plus progesterone). Naloxone (2mg/Kg decreased the reaction time of animals treated with adrenal and gonadal steroids (5.11 ñ 0.45 vs 4.15 ñ 0.44 and 5.04 ñ 0.43 vs 3.87 ñ 0.28 s, respectively, before and after naloxone) but failed to decrease it in rats treated with dexamethasone only (3.88 ñ 0.18 vs 4.34 ñ 0.25 s, before and after naloxone). These observations indicate that gonadal steroids are the most important steroid factors involved in the reaction time to tail immersion in hot water and confirm other reports that the opioid pathways modulating the neuronal circuitry require the presence of these hormones

The effect of tubero-infundibular dopaminergic neurons on prolactin and alpha-melanocyte stimulating hormone release

The effect of tubero-infundibular dopaminergic neurons (TIDA) on the release of prolactin (PRL) and alpha-melanocyte stimulating hormone (alpha-MSH) was studied in median eminence-lesioned (MEL) male rats (N = 6-28). Plasma PRL and alpha-MSH levels were significantly elevated 2(86.1 ñ 19.8 and 505.1 ñ 19.1 ng/ml), 4(278.7 ñ 15.5 and 487.4 ñ 125.1 ng/ml), 7 (116.2 ñ 16.2 and 495.8 ñ 62.6 ng/ml) and 14 (247.3 ñ 26.1 and 448.4 ñ 63.8 ng/ml) days after MEL when compared to sham-operated control animals (55.5 ñ 13.4 and 56.2 ñ 6.1 ng/ml, repectively). MEL altered plasma PRL and alpha-MSH levels in a diffential manner, with 1.5-to5.0-fold increase in PRL and an 8.0- to 9.0-fold increase in alpha-MSH. The increase of alpha-MSH levels occured abruptly and remained constant from days 2 to 14. These observations indicate that TIDA plays an important role in the pituitary release of PRL and alpha-MSH and provide evidence that the release of the two hormones occurs in a differential manner

Involvement of beta-adrenergic receptors in the differential release of gonadotropins in acutely orchidectomized rats.

To determine the differential release of gonadotropins in acutely orchidectomized rats, a single injection of the beta-adrenergic blocker Bornaprolol (FM 24) was administered to the animals and plasma FSH and LH levels were determined. FM 24 produced low plasma FSH levels only when injected 16 h before starting the blood collection and had no effect on FSH levels at 0, 30 and 46 h after its administration. However, it produced low LH plasma levels at 0, 16 and 30 h after administration. These findings confirm that pituitary beta-adrenergic receptors are involved in plasma LH release and suggest that they could also be involved in the differential release of FSH/LH.

The effect of age on the pressor response produced by common carotid artery occlusion in conscious rats.

The pressor responses to 60 s of common carotid artery occlusion were studied in conscious male rats of different ages. Compared to rats at the age of 2 months, the initial peak and the maintained response in 6- 12- and 18-month old rats were well preserved. In 1-month old rats, both components were significantly depressed but in 24-month old rats only the initial peak of the pressor response was markedly attenuated. These findings demonstrate that age is an important factor in the response to common carotid artery occlusion which is more marked for the initial peak than the maintained response.

The role of opioids in the analgesic response of rats during the estrous cycle.

The analgesic response was evaluated by the tail immersion test in female rats during each phase of the estrous cycle. The reaction time (mean +/- SEM) for tail withdrawal from the hot water bath was faster during proestrus (5.78 +/- 0.28 s) and decreased significantly during estrus (5.31 +/- 0.30 s) and diestrus 1 (5.40 +/- 0.21 s). Blockade of opiate receptors with naloxone (2 mg/kg, ip) increased the sensitivity to the noxious stimulus only during proestrus (6.46 +/- 0.42 vs 5.02 +/- 0.41 s). These results suggest that the effects of gonadal steroids on nociception may involve an opioid pathway.

Pressor responses to common carotid occlusion in female rats: effects of gonadectomy and treatment with gonadal steroid hormones.

The pressor responses to common carotid occlusion were studied in conscious female rats throughout the estrous cycle, after gonadectomy and after gonadectomy followed by treatment with estrogen and progesterone. The initial peak pressor response was highest during proestrus and fell significantly over the remaining 3 days of the estrous cycle. The maintained pressor response was relatively unchanged throughout the cycle, except during diestrus 1 when it decreased markedly. Gonadectomy reduced and treatment with estradiol alone increased the initial pressor component, respectively. Treatment of gonadectomized rats with estradiol plus progesterone enhanced both components. These findings suggest that gonadal steroid hormones are important modulators of the pressor response to common carotid occlusion.

Role of opioid peptides in pulsatile release of gonadotropins and prolactin in the rat.

To determine the role of endogenous opioid peptides in the pulsatile release of gonadotropins and prolactin in the ovariectomized rat, the opiate receptor blocker, naloxone, was administered intravenously, and its effect on plasma FSH, LH and prolactin was determined by multiple sampling prior to and after injection. Naloxone produced a dose-related increase in plasma LH and to a lesser extent FSH and decreased prolactin levels in the experiment in which they were examined. Higher doses of naloxone produced a significant increase in plasma LH pulse amplitude and lengthened the interpulse interval with a consequent decrease in pulse frequency. Minimum values between pulses were also increased. There was no clear effect on FSH pulsations but pulses of prolactin were blocked. Intraventricular (third ventricle) injection of a specific anti beta endorphin antiserum (3 microliter) produced an initial decline followed by an elevation of LH but had no effect on plasma FSH. The normal rabbit serum control injections were without effect. It is hypothesized that initiation of LH pulses in the castrated rat may be related to a periodic removal of tonic beta endorphinergic tone.

Beta-adrenergic blockers decrease levels of luteinizing hormone in plasma of orchidectomized rats.

The beta-adrenergic antagonists, propranolol and bornaprolol (FM-24), at greater than 2 mg/kg (as [-] form) significantly depressed plasma levels of luteinizing hormone (LH) in orchidectomized rats. This occurred in the absence of consistently significant changes in interpulse intervals or amplitudes of pulsatile LH release. Nadirs of plasma LH decreased significantly even at low blocker doses, with a clear dose dependence for both drugs. The highly significant decrease of plasma LH induced by blocker dosages causing greater than 93% inhibition of beta-adrenergic binding in the anterior pituitary gland was shown to occur without significant changes in binding of specific ligands at pituitary dopamine receptors and hypothalamic alpha 1-adrenergic receptors. The above evidence indicates that beta-blockers may lower LH release in vivo at the level of pituitary beta-adrenergic receptors.

Effects of unilateral decortication on beta-adrenergic receptors in the remaining cortex and in the hypothalamus of female rats.

Many experiments have been performed to evaluate the physiological role of catecholaminergic mechanisms in gonadotropin release. The purpose of the present study was to determine the concentration of beta-adrenoreceptors in the remaining (right) cerebral cortex and in right and left hypothalamic halves of hemi-decorticated female rats which exhibited elevated plasma gonadotropin levels as observed previously. The density of beta-receptors was measured using a high-affinity beta-adrenergic ligand, iodocyanopindolol (ICYP). Scatchard estimates were obtained for maximum binding (Bmax fmol/mg of tissues) from pooled cerebral cortical and hypothalamic tissue of animals under several experimental conditions after hemi-decortication and sham operation. There was an increase in beta-adrenoreceptor density in the remaining (right) cerebral cortex at all times examined in hemi-decorticate in comparison with the sham-operated animals (7 days, +10.9%; 21 days, +8.4%; 90 days, +22%; and 90 days plus ovariectomy, +34.8%). The number of beta-adrenoreceptors in the right hypothalamic half in hemi-decorticates decreased at 21 days (-42.20%) and then increased at 90 days (+76.63%) and 90 days plus ovariectomy (+51.75%) when compared with the left hypothalamic half. At the same time there were no significant changes in the sham-operated animals when comparing the receptor density in the right and left hypothalamic halves, respectively. Thus, our results suggest a direct or indirect adrenergic pathway by which the left cortex can influence the right cortex and a crossed pathway to the contralateral hypothalamus changing adrenergic activity which can alter the beta-adrenergic receptor binding capacity in the hypothalamus.

Beta-adrenergic agonists increase amplitude of LH release in orchidectomized rats.

The role of intravenously (iv) injected adrenergic agonists in the pulsatile secretion of luteinizing hormone (LH) was examined in unanesthesized, freely behaving, castrated male rats. The alpha 2-adrenergic receptor agonist, clonidine (25 micrograms/kg), and the alpha 1-adrenergic agonist, (-)-phenylephrine (12.5 micrograms/kg), did not significantly alter pulsatile release of LH. The physiological beta 2-adrenergic receptor agonist, (-)-epinephrine (2.5 micrograms/kg), significantly increased the mean plasma concentrations of plasma LH and the amplitude of the LH pulses over a period of 70 min. The specific beta 2-receptor agonist, salmefamol, significantly increased the mean plasma concentrations of LH and especially the average amplitude of LH pulses over 70-80 min in a dose-related fashion following the injection of doses from 25 to 125 micrograms/kg. The frequency of LH pulses was not significantly increased by either agonist at any of the doses employed. Salmefamol-induced increases in plasma LH could be prevented by the beta-adrenergic blocker, bornaprolol (FM-24), in a dose-related manner. When injected together with synthetic LH-releasing hormone (400 ng/kg), salmefamol (125 micrograms/kg) significantly increased the mean plasma concentrations of LH over 70 min compared with values in controls receiving LH-releasing hormone only. The data support the concept that beta-agonists act on their receptors in the pituitary to facilitate LH-releasing hormone-induced discharge of LH.