Acute and chronic stress and the inflammatory response in hyperprolactinemic rats.

BACKGROUND/AIM: Prolactin (PRL), a hormone produced by the pituitary gland, has multiple physiological functions, including immunoregulation. PRL can also be secreted in response to stressful stimuli. During stress, PRL has been suggested to oppose the immunosuppressive effects of inflammatory mediators. Therefore, the aim of the present study was to analyze the effects of short- and long-term hyperprolactinemia on the inflammatory response in rats subjected to acute or chronic cold stress. METHODS: Inflammatory edema was induced by carrageenan in male rats, and hyperprolactinemia was induced by injections of the dopamine receptor antagonist domperidone. The volume of inflammatory edema was measured by plethysmography after carrageenan injection. Additionally, the effects of hyperprolactinemia on body weight and serum corticosterone levels were evaluated. RESULTS AND CONCLUSION: Five days of domperidone-induced hyperprolactinemia increased the volume of inflammatory edema. No differences in serum corticosterone levels were observed between groups. No significant differences were found among 30 days domperidone-induced hyperprolactinemic animals subjected to acute stress and the inflammatory response observed in chronic hyperprolactinemic animals subjected to chronic stress. The results suggest that short-term hyperprolactinemia has pro-inflammatory effects. Because such an effect was not observed in long-term hyperprolactinemic animals, PRL-induced tolerance seems likely. We suggest that short-term hyperprolactinemia may act as a protective factor in rats subjected to acute stress. These data suggest that hyperprolactinemia and stress interact differentially according to the time period.

Behavioral and endocrine changes induced by perinatal fenvalerate exposure in female rats.

Pyrethroid insecticides have recently been linked to endocrine disruption. Endocrine disrupting chemicals have been defined as exogenous agents that interfere with the synthesis, secretion, binding, action, or elimination of natural hormones in the body. Previous research conducted in our laboratory suggests that perinatal exposure to fenvalerate, a type-II pyrethroid, interferes with brain sexual organization in male pups, probably acting on a critical perinatal hormone-related period. In the present study we investigate the effects of maternal exposure to fenvalerate (FV) during the prenatal and postnatal periods of sexual brain organization of female offspring. Behavioral (open-field, stereotyped and sexual behaviors), physical (sexual maturation, body and uterine weights), and neuroendocrine (estrous cycle and gonadal hormone levels ) parameters were assessed. Results show that 1) sexual maturation was delayed, albeit body weight was unchanged until adulthood; 2) there was a reduction in sexual behavior; 3) the estrous cycle was abnormal, and the uterine weight at different phases of the estrous cycle was modified; 4) gonadal hormone levels in the plasma were not affected, neither was stereotypy nor open-field behaviors. These results were attributed to an anti-estrogenic effect of perinatal exposure to FV during the critical periods of female brain sexual organization.

Reproductive experience modulates dopamine-related behavioral responses.

Reproductive experience (RE), i.e., mating, pregnancy, parturition and lactation, has long-term physiological effects. It reduces the basal levels of circulating prolactin in parous women, decreases the intensity of nocturnal and diurnal prolactin surges in multigravid rats during early pregnancy, as well as the hormonal and neurochemical responses to the dopamine receptor antagonists metoclopramide and haloperidol. In the present study, we evaluated the possible influences of RE on some dopaminergic-related behaviors: (1) acute responses to a new environment represented by an open-field arena plus injection stress; (2) modulation of behavior after a short-term withdrawal subsequent to 7 days amphetamine (AMPH) pretreatment; (3) stereotypy elicited by AMPH and apomorphine (APO); and (4) APO-induced hypothermia. In the 3-min open-field test, there was a decrease in locomotor activity as a function of RE. Behavioral depression was mild and AMPH pretreatment revealed RE alterations. APO-induced stereotyped behavior was slightly more intense in primiparous animals, although no significant differences were found in AMPH-induced stereotyped behavior. No differences were observed between intact and ovariectomized primiparous and nulliparous animals in APO-induced hypothermia. Our data suggest that RE modifies some DA-related behavioral responses. The physiological relevance of the phenomenon is discussed.

Perinatal fenvalerate exposure: behavioral and endocrinology changes in male rats.

The effects of maternal exposure to fenvalerate during the prenatal and postnatal periods of sexual brain differentiation were studied in adult male offspring. Behavioral (open field, stereotyped, and sexual behaviors), physical (sexual maturation, body and organ weights), endocrine (testosterone levels), and neurochemical (striatal and hypothalamic monoamine and respective metabolite levels) data were assessed. The results showed that there was no change in the age of testis descent or testis weight, nor were there changes in monoamine levels or stereotyped behavior. However, there were significant reductions in ductus deferens and seminal vesicle weights and plasma testosterone concentrations. In addition, treated offspring showed decreased male sexual behavior and increased immobility in the open field. These results indicate that perinatal exposure to fenvalerate during the critical periods of male brain sexual differentiation has long-term effects on the reproductive physiology and behavior of male rats.

Dual modulation of male sexual behavior in rats by central prolactin: relationship with in vivo striatal dopaminergic activity.

Prolactin (PRL) appears to be localized in several brain structures. Central, behaviorally meaningful, neural actions of this protein have been demonstrated in a large number of studies. The present report describes sexual behavioral and in vivo neurochemical data obtained from adult male rats injected intracerebroventricularly acutely (10 micrograms) or chronically (5 days; 10 micrograms/day) with ovine prolactin (oPRL). The extracellular striatal concentrations of dopamine and serotonin metabolites were estimated by HPLC measurements in microdialysis perfusates. A single (10 micrograms) administration of oPRL facilitated sexual activity and increased extracellular striatal DOPAC, HVA and 5HIAA levels, whereas five daily intracerebroventricular injections of oPRL, decreased the sexual behavior and reduced DOPAC and HVA striatal extracellular concentrations in response to a central oPRL injection. These results show that acute and chronic central oPRL treatments have stimulatory and inhibitory effects on male sexual behavior, respectively. In addition, the results suggest that striatal dopaminergic activity is increased and decreased by acute and 5-day central oPRL treatments. These data suggest that behavioral effects of PRL occur simultaneously with changes in striatal dopaminergic activity.

Reproductive experience reduces striatal dopaminergic responses in freely moving female rats.

Reproductive experience influences basal and pregnancy profiles of circulating prolactin levels in women and female rats, respectively. Endocrine responses to dopaminergic antagonists are modified by reproductive experience as well. Striatal extracellular dopamine metabolites were measured in vivo by HPLC-ED in perfusates obtained by microdialysis in non-anaesthetized, freely moving, intact and ovariectomized, nulliparous and primiparous rats. Data were collected for at least 7 h. This period always included the light-dark shift at 18:00 h. In a second experiment, microdialysis was performed in ovariectomized nulliparous and primiparous rats treated with haloperidol (1.0 mg/kg s.c.). During the 1 h before and after the onset of the light-dark shift, HVA concentrations in the perfusates increased in nulliparous compared with primiparous rats. The haloperidol-induced increase in DOPAC and HVA was less intense in primiparous rats than that in nulliparous ovariectomized rats. These data revealed a different pattern of striatal dopaminergic anticipation and response to the shift in the light-dark cycle in nulliparous as compared with primiparous intact females. In addition, a distinct striatal dopaminergic response to haloperidol was observed in primiparous as compared to nulliparous ovariectomized rats. The results suggest that reproductive experience can modulate the activity of dopaminergic terminals in the striatum.

Reproductive experience increases striatal and hypothalamic dopamine levels in pregnant rats.

The effects of parity on the dopaminergic function of rats were studied. Striatal and hypothalamic levels of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), norepinephrine (NE), serotonin (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) as well as serum prolactin (PRL) levels of 7-days primigravid and multigravid rats were compared. Brains and trunk blood were collected from 1200-1400 h on day 7 of pregnancy and assayed for monoamines and their metabolites, and prolactin, respectively. Multigravid rats showed a significant increase in striatal and hypothalamic dopamine levels. A tendency to increase in striatal DOPAC levels was also observed in multigravid rats. Levels of other neuro-transmitters and metabolites were not statistically different. Haloperidol (1 mg/kg) treatment induced a significant increase in multigravid 5-HT striatal levels. There was no statistical difference among primigravid and multigravid serum PRL levels after either saline or haloperidol treatment. These data suggest that prior parity produces a shift in dopaminergic activity in multigravid rats.