George A. Mason

Oxytocin activates the postpartum onset of rat maternal behavior in the ventral tegmental and medial preoptic areas.

Oxytocin binding (Bmax) was found to be higher in the ventral tegmental area (VTA) and the medial preoptic area (MPOA) at midparturition compared with Pregnancy Days 15-17 or Postpartum Days 5-7 in rat dams. Pup retrieval and assuming a nursing posture over pups were blocked in parturient dams by infusions of an oxytocin antagonist into the VTA or MPOA and by infusions of a vasopressin (V1) antagonist into the MPOA. These results implicate oxytocin in the VTA and MPOA and vasopressin in the MPOA, as well as a parturition-associated rise in oxytocin binding in these sites in the postpartum activation of maternal behavior.

Ischemic but not thermal pain sensitivity varies across the menstrual cycle

Objective and Method Findings from both animal and human research suggest that pain sensitivity changes across the menstrual cycle; however, among humans the nature of these menstrual cycle effects remains unclear. The present study used a repeated-measures design to evaluate changes in thermal and ischemic pain responses during three phases of the menstrual cycle, midfollicular (postmenstrual), ovulatory, and mid-to-late luteal (premenstrual), in 11 healthy women. The cycle phase during which subjects began their participation was determined randomly. Plasma levels of estrogen, progesterone, luteinizing hormone (LH), testosterone, and beta-endorphin were determined at each experimental session. Participants also completed a daily diary of physical and emotional symptoms for two complete menstrual cycles before the experimental sessions. Results The results indicated that women showed less ischemic pain sensitivity during the midfollicular compared with the ovulatory and mid-to-late luteal phases, but thermal pain responses did not vary significantly across menstrual cycle phases. Physical and emotional symptoms were minimal and did not change significantly across the menstrual cycle. Conclusions These findings indicate greater ischemic but not thermal pain sensitivity among women after the midcycle LH surge. The practical relevance and potential mechanisms of these findings are discussed.

Effects of Chronic Mild Stress on Serum Complement Activity, Saccharin Preference, and Corticosterone Levels in Flinders Lines of Rats

Complement proteins and fragments participate in the induction and modulation of specific and nonspecific immune reactions. We have examined the effect of 4 weeks of chronic mild stress (CMS) on complement sheep red blood cell hemolytic activity measured in CH50 units in two selectively bred lines of rats, the Flinders resistant line (FRL) and the Flinders sensitive line (FSL), that differ in cholinergic sensitivity and behavioral characteristics. Additionally, CMS-induced hedonic deficit (decreased preference for 0.02% saccharin over water) and serum corticosterone levels were compared in FRL and FSL rats. CMS caused a significantly (p < 0.01) greater decline in CH50 responses in FSL (-15%) than in FRL (-7%) rats. This was accompanied by a significant (p < 0.01) suppression of saccharin preference over a 24 h period in both FRL and FSL rats. Both lines showed a similar, more than 2-fold (p < 0.01) increase in corticosterone levels following CMS. These results further confirm that CMS induces a depressive-like state in rats as well as the validity of the FSL rat as a genetic model of depression. They also indicate that the effect of stress on the immune system can be monitored by measuring the complement CH50 response.

Enhancement of ethanol-induced sedation and hypothermia by centrally administered neurotensin, β-endorphin and bombesin

Abstract Intracisternal administration of three endogenous neuropeptides (neurotensin, β-endorphin, or bombesin) potentiated the duration of sedation induced by a fixed dose of ethanol (5.2 g/kg) in mice. The minimally effective dose of each peptide that enhanced ethanol-induced sedation was: neurotensin, 0.18 nmoles; β-endorphin, 1.79 nmoles; and bombesin, 0.06 nmoles. The enhancement of ethanol-induced sedation was correlated with the potentiation of ethanol-induced hypothermia for all three peptides. None of the neuropeptides studied significantly altered blood or brain ethanol concentrations, suggesting that the observed effects were not due to differences in ethanol metabolism.

Thyroid and adrenal measures during late pregnancy and the puerperium in women who have been major depressed or who become dysphoric postpartum

Prior studies of thyroid, adrenal and mood measures during pregnancy and the puerperium, which we review, have not examined hormone-mood relationships over the full peripartum period during which hormone levels change nor have they compared prior depression history with hormone changes. In a pilot study we measured thyroid and adrenal hormones as well as mood at 38 weeks of pregnancy, and 1, 3, 6, 9 and 12 weeks postpartum in 12 women with major depression history and 14 women with negative psychiatric history. Subjects with prior depressions had significantly higher T3, T4, TSH and cortisol levels during the puerperium. Subjects with higher levels of postpartum dysphoria had lower T4 and free T4 levels as well as higher T3 uptake at 38 weeks of pregnancy and higher cortisol levels during the puerperium. The pathophysiological implications of these findings are discussed.

Treatment of depression in cancer patients is associated with better life adaptation: a pilot study.

&NA; Major depression occurs in a significant number of cancer patients, and there is evidence that cancer patients with depression do not receive adequate antidepressant treatment. In an uncontrolled pilot study, the authors assess the degree of depression and the quality of life after the initiation of antidepressant medication treatment in 12 depressed cancer patients who received adequate antidepressant drugs and in 10 depressed cancer patients who received inadequate antidepressant treatment. These preliminary findings suggest that cancer patients with major depression benefit from antidepressant medication treatment and may experience an improved psychosocial adjustment to cancer. Controlled clinical trials will be necessary to verify these preliminary findings.

Marked Reduction in Gonadal Steroid Hormone Levels in Rats Treated Neonatally with Monosodium L-Glutamate: Further Evidence for Disruption of Hypothalamic-Pituitary-Gonadal Axis Regulation

Serum levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin, estradiol-17 beta and testosterone were determined in adult rats that were treated in the neonatal period with monosodium L-glutamate (MSG) which has previously been shown to reliably produce destruction of arcuate nucleus perikarya. MSG-treated males had significantly smaller accessory sexual organs (seminal vesicles and ventral prostate) and tests and had significantly lower serum concentrations of FSH and testosterone than sex-matched controls. MSG-treated females had significantly lower serum concentrations of LH, FSH and estradiol-17 beta. Prolactin levels of MSG-treated rats were no different than sex-matched controls. This marked reduction in gonadal steroid levels (decreases 68%) and inappropriately low gonadotropin levels further characterizes the deficit of feedback regulation in the hypothalamic-pituitary-gonadal axis in MSG-treated rats.

Prevalence of antithyroid antibodies in mood disorders

We examined the prevalence of antimicrosomal and antithyroglobulin antibodies in psychiatric inpatients with unipolar depression (N = 218), bipolar disorder manic (N = 51), bipolar disorder depressed (N = 19), and bipolar disorder mixed (N = 26) in comparison with two control groups: psychiatric inpatients with adjustment disorder (N = 80) and family medicine outpatients without current psychiatric illness (N = 144). A statistical analysis that controlled for age and sex revealed the frequency of positive antibody titers not to be increased in patients with a diagnosis of unipolar depression (6.9%) or bipolar disorder manic (3.9%), when compared with patients with adjustment disorder (2.5%) and non‐psychiatric subjects (6.9%). There was a weak trend toward an increased prevalence of antithyroid antibodies in patients with bipolar disorder, mixed (19%) or depressed subtype (16%). The excess occurrence of antibodies in patients with either mixed or depressed bipolar disorder did not appear to be related to lithium exposure, which was similar in all bipolar subgroups. When the intervening influences of age and sex are taken into account, unipolar depression does not appear to be associated with an excessive rate of antithyroid antibodies; however thyroid autoimmunity may be weakly associated with subtypes of bipolar disorder in which depressive symptoms are prominent. Depression and Anxiety 5:91–96, 1997.

L-triiodothyronine: is this peripheral hormone a central neurotransmitter?

L-triiodothyronine (T3) has previously been shown to substance fast-phase, depolarization-induced 45Ca uptake and [3H-gamma-aminobutyric acid release by rat brain synaptosomes at low nanomolar concentrations comparable to those reported for whole brain. Neverthless, the physiologic importance of these nonnuclear-mediated effects of T3 has remained uncertain, a part because specific mechanisms and the presence of T3 at pesumptive sites of action have not been demonstrated. Isotopic studies showing that L-tetraiodothyronine thyroxine, T4) and T3 are concentrated in synaptosomes, and that T4 is deiodinated to T3 suggested that endogenous levels of T3 in nerve terminals are probably much higher than in other compartments of the brain. In the present study we confirmed that endogenous levels of T3 in nerve terminals are at least eightfold higher, and may be as much as 60-fold higher, than in whole brain. More importantly, we showed that both 125I-labeled T3 and endogenous T3, but not 125I-T4 or endogenous T4, are released from depolarized synaptosomes, primarily by a Ca2+-dependent process. This demonstrates a mechanism for raising the level of T3 within the synapse, where the hormone may interact with pre- and postsynaptic binding (or uptake) sites, and suggests that the peripheral hormone T3 may be a neurotransmitter.

Estrogen increases affinity of oxytocin receptors in the medial preoptic area-anterior hypothalamus

Analysis of binding data from saturation experiments using a radiolabeled oxytocin antagonist ([125I]OTA) demonstrated an increase in binding affinity after treatment with 5 micrograms estradiol benzoate (EB) for 3 days in membrane fractions from the medial preoptic area-anterior hypothalamus (MPOA-AH) of ovariectomized (OVX) rats. Analysis of data from competition experiments revealed high- and low-affinity [125I]OTA binding sites in the MPOA-AH, the medial basal hypothalamus (MBH), and hippocampus of OVX controls. Three days of EB treatment reduced low-affinity binding sites in the MPOA-AH and MBH, but not in the hippocampus. Treatment of membrane fractions from the MPOA-AH of oil-treated OVX rats in vitro with 100 nM OT or with estrogen or progesterone conjugated to bovine serum albumin (E-BSA and P-BSA) also reduced low-affinity [125I]OTA binding sites but BSA alone did not.