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C A Pedersen

Publications and source records attributed to C A Pedersen.

At least 91 records · Page 5Linked to original sources

Estradiol influences oxytocin-immunoreactive brain systems.

The rat brain was examined immunocytochemically for estrogen-dependent changes of oxytocin immunoreactivity at the light microscopical level. Ovariectomized rats were treated with subcutaneous silastic implants with estradiol, or empty implants as controls for 2 days (short term treatment). Another group of rats was injected weekly for 2 months with 1 mg estradiol (long term, high dose treatment). After perfusion fixation serial Vibratome sections were stained with antibodies to oxytocin. In control animals, oxytocin immunoreactive perikarya were found in the magnocellular hypothalamic nuclei. Accessory oxytocin neurons appeared in various hypothalamic sites: immunostained neuronal processes were visible in the preoptic region, the lateral septum, the ventromedial hypothalamus and the median eminence. In short term estradiol treated animals, additional immunoreactive perikarya could be observed in the septohypothalamic nucleus, the lateral subcommissural area, the medial preoptic area, the perifornical region, the zona incerta and the ansa lenticularis. An increased number of immunostained fibers was found in the lateral septum, the preoptic region, the striatum and the amygdala. Animals treated with high doses of estradiol for 2 months showed oxytocin immunostaining only in the paraventricular and supraoptic nuclei and in the median eminence. The distribution of oxytocin immunoreactive neurons in the magnocellular nuclei did not change with changing estradiol levels. Physiological amounts of estrogen given for 2 days increased the number of oxytocinergic neurons visible outside the classical magnocellular nuclei while prolonged, high dose estrogen treatment diminished immunostaining in these oxytocinergic systems.

Animals↗

Effects of nonapeptide antagonists on oxytocin- and arginine-vasopressin-induced analgesia in mice.

Several peptides, including arginine-vasopressin (AVP), neurotensin, and substance P, produce analgesia that is not mediated by opiate systems. Using the hot plate test, we studied the analgesic effects of intracisternal (i.c.) administration of various doses of the nonapeptide oxytocin (OXY) in Swiss-Webster mice. We found that OXY (1-4 micrograms) significantly increased the latency of animals to jump or lick their paws after placement on a hot plate. This effect was not blocked by naloxone pretreatment, which suggests that it is not opiate dependent. Using the hot plate test, we confirmed that AVP (1 and 4 micrograms) also produces analgesia. We then studied the analgesia produced by OXY and by AVP using 3 nonapeptide analogues with antagonist properties: [Pen1, LpMePhe2, Thr4, Orn8]OXY (PLMPTO-OXY) that has anti-oxytocic properties in the uterine contraction assay, d(CH2)5Tyr(Me)AVP(dTM-AVP) which antagonizes the antidiuretic properties of AVP and d(CH2)5D-Ile2,Abu4-AVP (dIA-AVP) which antagonizes the vasopressor effects of AVP. Simultaneous administration of PLMPTO-OXY completely blocked the analgesia produced by OXY whereas the antidiuretic antagonist dIA-AVP partially blocked OXY-induced analgesia and dTM-AVP had no effect. None of the antagonists used blocked AVP-induced analgesia. We concluded that the neural systems mediating the analgesic effects of i.c. OXY differ from those for AVP.

Analgesia↗

Use of the dexamethasone suppression test with DSM-III criteria in psychiatrically hospitalized adolescents.

Although developmental factors may complicate the assessment of major affective disorder in the adolescent patient, studies suggest that the same descriptive criteria used in the assessment of the adult patient can be utilized to diagnose major depression in the adolescent patient. In order to determine if the dexamethasone suppression test (DST) has a similar sensitivity and specificity for DSM-III major depression in adolescents compared to that found in adult patients, we administered the DST to 55 adolescents admitted to an inpatient psychiatric unit. Each of the adolescents exhibited depressive symptoms; 23 fulfilled DSM-III criteria for major depressive syndromes (20 major depression; 3 schizoaffective), and 32 fulfilled the criteria for other DSM-III diagnoses. Of the 23 patients with major affective disorder, 10 (43%) exhibited nonsuppression of serum cortisol after dexamethasone. Of the 32 patients with depressive symptoms and other diagnoses, five (16%) exhibited nonsuppression; on follow up, three of the five nonsuppressors fulfilled criteria for major depression. These findings suggest that DSM-III criteria can be used to diagnose major depression in the adolescent patient and that the DST may play an important role in detecting or confirming the diagnosis of major depressive disorders in adolescent patients.

Adolescent↗

Oxytocin and vasopressin immunoreactivity in hypothalamic and extrahypothalamic sites in late pregnant and postpartum rats.

This study examines immunoreactive levels of oxytocin (OT) and arginine-vasopressin (AVP) from acid extracts of the paraventricular nucleus (PVN), supraoptic nucleus (SON), anterior commissural nucleus (ACN) and the suprachiasmatic nucleus (SCN) as well as selected extrahypothalamic sites in pregnant or postpartum (PP) rats. Animals are sacrificed between 08.30 and 10.30 h 16 or 22 days after sperm is detected in their vaginal smears or on the morning after parturition. Peptide levels of pregnant or PP animals are compared to levels of ovariectomized (OVXed) rats sacrificed and assayed simultaneously. OT immunoreactive levels in the PVN and SON are significantly elevated in late pregnancy and PP. OT content of the ACN is elevated on day 16, but drops to control levels by day 22 of pregnancy and day 1 PP. Concomitant with the falling OT content in the ACN at the end of pregnancy, samples from the ventral septum have significantly increased OT content on day 1 PP. In extracts including the nucleus of the tractus solitarius (NTS) and dorsal motor nucleus of the vagus (dMX) OT is also elevated on the day after parturition. AVP levels peak on the day before parturition in all hypothalamic nuclei examined. These increases are significantly greater than in OVXed controls in the PVN and SON. AVP levels in the lateral habenula are elevated both on day 16 of pregnancy and on the first day PP. From these data we conclude that nonapeptide levels are altered across late pregnancy and early postpartum in some hypothalamic synthesis sites and in certain limbic and brainstem sites. We also postulate that OT is transported out of the ACN to extrahypothalamic sites around the time of parturition.

Animals↗

Variations in concentration of oxytocin and vasopressin in the paraventricular nucleus of the hypothalamus during the estrous cycle in rats.

Oxytocin (OT) and arginine-8-vasopressin (AVP) were measured by radioimmunoassay in micropunched hypothalamic neurosecretory nuclei of estrous cycling female Sprague-Dawley rats. In the paraventricular nucleus (PVN): the concentration (pg/microgram protein) of OT was significantly higher in rats in diestrus than during proestrus, estrus, or metestrus, while the concentration during metestrus was significantly greater than in proestrus and estrus; the concentration of AVP was significantly lower in animals in estrus than during the other three stages; because the paraventricular OT levels dropped before proestrus, the AVP/OT ratio was significantly greater in animals in proestrus than in diestrus, metestrus, and estrus. In the supraoptic nucleus (SON) a similar trend was noted: the concentration of OT was highest during diestrus, and AVP was lowest during estrus, though neither was significantly different from other stages. Because the OT and AVP cycles in the SON were asynchronous, the ratio of AVP to OT was significantly higher in proestrus than in metestrus or diestrus and significantly greater in estrus than during diestrus. In contrast to these two areas, peptide concentrations did not vary significantly across the estrous cycle in other sites of nonapeptide synthesis, i.e. the anterior commissural nucleus (ACN) and the suprachiasmatic nuclei (SCN).

Animals↗

Oxytocin potently enhances novelty-induced grooming behavior in the rat.

Intracerebroventricular (i.c.v.) injection of oxytocin was followed by an enhancement of novelty-induced grooming in male and female rats. This effect was dose-dependent, in a dose range of 0.1-10 micrograms. Grooming activity of rats injected i.c.v. with 10 micrograms of oxytocin was 9-fold higher than that of saline-injected controls. The analysis of behavioral element composition revealed an increased occurrence of genital grooming in oxytocin-injected rats. A time-course study revealed a sustained increase in grooming activity of oxytocin-treated rats during 45 min of behavioral testing. Intraperitoneal (i.p.) injection of the dopamine antagonist, haloperidol, totally suppressed oxytocin-enhanced grooming. Furthermore, i.p. injection of the opiate receptor antagonist, naloxone, was followed by an attenuation but not a suppression of grooming enhanced by i.c.v. administration of oxytocin. In addition, a small but significant increase in grooming activity was observed after subcutaneous injection of oxytocin. These results suggest that oxytocin-enhanced grooming behavior involves central mechanisms, e.g. dopamine and opioid transmission in the brain.

Animals↗

Dopamine neurotransmission in the nucleus accumbens may be involved in oxytocin-enhanced grooming behavior of the rat.

Intracerebroventricular (ICV) infusion of a low dose of oxytocin enhanced novelty-induced grooming in male rats. The present experiments were undertaken to investigate whether dopamine neurotransmission in the nucleus accumbens is involved in this effect. Bilateral lesions of the nucleus accumbens by microinjections of 6-hydroxydopamine (6-OHDA) totally prevented the enhancement of grooming behavior after subsequent ICV infusion of oxytocin. Furthermore, bilateral injections of the dopamine receptor antagonist, haloperidol, into the nucleus accumbens completely suppressed grooming behavior of rats infused ICV with oxytocin. These results suggest that dopamine neurotransmission in the nucleus accumbens is involved in the behavioral response enhanced by the peptide.

Animals↗

Is oxytocin-induced grooming mediated by uterine-like receptors?

In this study, we examined whether the mechanisms mediating the induction of grooming behavior by oxytocin (OT) is similar to mechanisms mediating the effects of OT on uterine contractility. Sprague-Dawley strain female rats were injected intracerebroventricularly (ICV) with OT or OT analogues and then were observed for grooming behaviors 25 minutes later for 30 minutes. The uterotonic analogue deamino-OT injected ICV at equimolar doses to 1 microgram OT significantly elevated grooming scores although less than did OT. Other agonist analogues were not effective in inducing an increase in grooming behavior. The simultaneous ICV injection of the analogue [Pen1, Phe2, Thr4, delta 3, 4Pro7, Orn8]-OT, which blocked the effects of OT on uterine contractility, also blocked the effect of OT on grooming behavior. Injection of the same dose of this antagonist analogue did not effect the increased grooming behavior after AVP injection. Pretreatment with 5 mg/kg of the prostaglandin synthetase inhibitor indomethacin significantly inhibited OT-induced grooming. We have concluded from these data that the mechanism underlying the effect of OT on grooming is similar to its effects on uterine contractility in some respects. However, observations that the OT antagonist analogue blocked OT- but not AVP-induced grooming may suggest that more than one receptor or mechanism exists by which nonapeptides initiate excessive grooming.

Animals↗

Interactive effects of intracisternal oxytocin and other centrally active substances on colonic temperatures of mice.

Oxytocin (OXY) administered intracisternally to adult male mice produced a significant dose-related (1-4 micrograms) increase in colonic temperatures at an ambient temperature of 25 degrees C. The maximal rise in temperature occurred 30 min after administration of the peptide. The interactive effects on colonic temperature of central OXY with equimolar amounts of neurotensin, bombesin or beta-endorphin or of 2 2 mg/kg of chlorpromazine were investigated. OXY significantly antagonized the hypothermia produced by all of these substances. Pretreatment of mice with haloperidol or naloxone failed to prevent OXY-induced hyperthermia. The hyperthermic action of OXY and the interactive effects of OXY with other peptides on thermoregulation may be physiologically significant during parturition and lactation.

Animals↗

A comparison of grooming behavior potencies of neurohypophyseal nonapeptides.

We have previously demonstrated that intracerebroventricular (ICV) administration of oxytocin (OXY) enhanced grooming behaviors in male and female rats at a 1 microgram dose. In the present study female rats were injected ICV with 1 microgram OXY or equimolar doses of other peptides. At this dose arginine-vasopressin (AVP), arginine-vasotocin (AVT) and lysine-vasopressin (LVP), as well as alpha-MSH, were as effective as OXY in increasing grooming behavior. At equimolar doses, ACTH1-10, tocinoic acid (the ring structure of OXY) and Pro-Leu-Gly-NH2 (the tail structure of OXY) had no significant effect on grooming behavior. The potency of AVP and AVT was determined across a 0.05-5 microgram dose range. Grooming scores increased in an apparent linear manner across a similar OXY dose range. Both AVP and AVT, however, manifested an inverted U grooming response curve. Maximum grooming scores resulted from a 0.1 microgram dose of AVT or a 0.5 microgram AVP dose. Analyses of the aspects of grooming separately found that nonapeptides OXY, AVP and AVT all elevated body grooming, washing, and scratching. Because AVT and AVP administration resulted in grooming scores significantly higher than OXY at lower doses, we concluded that the CNS is more sensitive to the effects of AVT and AVP on grooming behavior than OXY.

Adrenocorticotropic Hormone↗

Appearance of mania in drug-resistant bipolar depressed patients after treatment with L-triiodothyronine.

L-Triiodothyronine (T3) has been reported to potentiate the antidepressant effects of tricyclic antidepressants (TCAs) in patients who do not respond to these drugs, while thyroxine (T4) has been used to treat rapid-cycling bipolar disorder patients. The development of mania in antidepressant-resistant bipolar depressed patients after T3 was added to their antidepressant treatment is reported. It is speculated that thyroid hormone-catecholamine receptor interaction might underlie these T3-associated clinical manifestations. It is concluded that T3 did not prevent the switch to mania in the bipolar depressed patients reported here. Further study is necessary to determine if T3 plays a role in promoting the switch to mania in depressed patients treated with T3 in conjunction with TCAs, and if bipolar depressed patients are particularly vulnerable to mania from the combined effects of TCAs and T3.

Adult↗

Oxytocin antiserum delays onset of ovarian steroid-induced maternal behavior.

We have previously reported that intracerebroventricular (ICV) administration of oxytocin (OXY) produces a significant increase in maternal behavior in ovariectomized (OVXed) rats given a single priming dose of estrogen. Arginine vasopressin (AVP) has a weaker and more delayed but significant facilitating effect on the onset of maternal behavior. Other investigators have demonstrated that prolonged treatment of OVXed nulliparous rats with estrogen and progesterone followed by withdrawal of progesterone shortens the latency of onset of maternal behavior. We hypothesized that ovarian steroids increase the onset of maternal behavior by a central mechanism involving OXY and possibly AVP. To test this nulliparous Sprague Dawley rats were given SC one Silastic capsule containing 4.4 mg of 17 beta-estradiol eight days after OVX and three capsules each containing 40 mg of progesterone ten days after OVX. Progesterone capsules were removed on the 20th day after OVX, 24 hrs before the introduction of three rat pups (1-5 days old). One hr prior to introduction of pups animals received ICV 10 microliters of anti-oxytocin antiserum (AOA), anti-arginine vasopressin antiserum (AVA), anti-neurotensin antiserum (ANA), normal rabbit serum (NRS), AOA + 250 ng OXY or no ICV infusion. Animals receiving AOA displayed significantly less maternal behavior compared to animals receiving NRS, ANA or no ICV infusion over the first two, six and 25 hrs of pup contact. OXY significantly reversed the inhibitory effect of AOA in the first two hrs of pup contact. AVA significantly decreased the onset of maternal behavior compared to ANA or no ICV infusion over the first six hrs of pup contact.

Animals↗

Oxytocin induces maternal behavior in virgin female rats.

Intracerebroventricular administration of oxytocin to virgin female rats that had been ovariectomized and primed with estrogen 48 hours previously induced a rapid onset of full maternal behavior. The maternal behavior persisted and its incidence was dose-related. Tocinoic acid, the ring structure of oxytocin, also rapidly induced the onset of persistent, full maternal behavior. Arginine vasopressin induced persistent maternal behavior, but this behavior had a later onset. Prostaglandin F2 alpha induced strong partial maternal behavior, which showed early onset but did not persist. Many other peptides, ovarian steroids, and prostaglandin E2 were no more effective than saline. These findings suggest that the release of oxytocin and prostaglandin F2 alpha during labor may promote maternal behavior in rats.

Animals↗

Induction of maternal behavior in virgin rats after intracerebroventricular administration of oxytocin.

Oxytocin produces uterine contractions and milk ejection, functions related to parturition and nuturing. Studies were conducted to determine if this peptide, native to the brain and the posterior pituitary gland, plays a role in the induction of maternal behavior. Intact virgin female rats were given 0.4 mug of oxytocin, 0.4 mug of [Arg(8)]vasopressin, or saline through lateral ventricular cannulae. Forty-two percent of intact rats receiving oxytocin displayed full maternal behavior towards foster pups. None of the saline- or vasopressin-treated animals displayed full maternal behavior. Criteria in five behavioral categories had to be fulfilled by an animal within 2 hr of injection for its behavior to be considered fully maternal. When partial maternal responses were considered, oxytocin was significantly more effective than saline and marginally more effective than vasopressin. Five animals responding fully maternally after oxytocin injection were allowed to stay with pups for 10 days. All five continued to display full maternal behavior during this time. Nearly all animals that responded fully maternally to oxytocin injection were in the last day of diestrus or in proestrus or estrus. This suggested that elevated or recently elevated levels of estrogen may be necessary for the induction of full maternal behavior by oxytocin. Twenty-seven virgin female rats were ovariectomized and given either 100 mug of estradiol benzoate per kg in oil subcutaneously or oil alone immediately after operation. Forty-eight hours later, all animals received 0.4 mug of oxytocin intracerebroventricularly. Eleven of 13 estrogen-primed animals became fully maternal; none of 14 nonprimed animals became fully maternal.

Animals↗

Oxytocin facilitates the sexual receptivity of estrogen-treated female rats.

Oxytocin (OXY) and arginine-vasopressin (AVP) are widely distributed within the brain and have a number of behavioral effects resulting from central administration. We have previously found that central OXY administration accelerated the onset of maternal behavior in ovariectomized (OVXed) estrogen-treated nulliparous rats. We now report that intracerebroventricular (ICV) injections of OXY enhance lordosis behavior in OVXed estrogen-treated rats. After treatment with 0.15, 0.20, or 0.25 micrograms EB IM for three days, OXY (800 ng) infusion ICV on the fourth day produced a significant increase in lordosis behavior between 20 and 90 minutes after administration. Doses of OXY between 0.8 and 5 micrograms injected ICV significantly increased lordosis behavior in animals pretreated with 0.5 micrograms EB for three days. In other OVXed rats treated with 0.5 micrograms EB for three days, ICV injections of 1 micrograms OXY or an equimolar dose of AVP significantly increased lordosis while equimolar doses of ACTH1-10, ACTH4-10, arginine-vasotocin, GnRH and alpha-MSH did not significantly increase lordosis behavior over saline vehicle levels. ACTH1-24 significantly lowered lordosis quotients. We have concluded from these data that central administration of OXY (and possibly AVP) enhance female sexual receptivity. This effect is estrogen dependent, dose related and under our test conditions, specific to OXY and AVP.

Animals↗