Kavita Gulati

The amygdaloid complex, corticotropin releasing factor and stress-induced gastric ulcerogenesis in rats.

The amygdaloid complex and corticotropin releasing factor (CRF) are both important in stress reactions and we thus evaluated the effects of intra-amygdalar CRF on stress ulceration in rats. Bilateral micro-applications of CRF (0.05, 0.5 or 5.0 micrograms) into the central amygdala (CEA) attenuated cold restraint-induced gastric mucosal lesions in a dose-related manner. Similar gastric cytoprotective effects were seen with intra-CEA noradrenaline (NA; 3.0 micrograms), whereas the NA neurotoxin, DSP-4 (25 micrograms), or the beta-adrenoceptor antagonist, propranolol (1 microgram), aggravated stress ulcer pathology. Intra-CEA pretreatment with DSP-4 or propranolol clearly reversed the ulceroprotective effects of CRF during stress. These results indicate that the CEA is a neural substrate for CRF effects, and CRF-NA interactions in this limbic area are crucial for the regulation of stress ulcerogenesis.

Effects of acute and chronic morphine on food intake in rats: Modulation by oxytocin and vasopressin

The effects of acute and chronic morphine administration and the interaction with oxytocin and vasopressin on food intake response were investigated at various intervals during a 24-h schedule in rats. Acute morphine (5 mg/kg, IP) produced a generalized hyperphagic effect in both light (0-6 h) and dark (6-24 h) phases, the most marked effects being at 0-1 h, 1-3 h and 6-24 h. Chronic morphine (7 days) in an escalating dose schedule (5-35 mg/kg/day) produced (a) an enhancement of the hyperphagic effect in the light phase and (b) an attenuation of the food intake response during the dark phase. Neither oxytocin nor vasopressin had any significant influence on food intake, per se, after either acute or chronic administrations. However, both OXY and AVP reduced the hyperphagic response to acute morphine throughout the 24-h observation period. Further, on chronic administration, both neurohypophyseal peptides blocked the enhancements of morphine-induced hyperphagia (reverse tolerance) during light phase, whereas only vasopressin was effective in attenuating the reduction of hyperphagia (tolerance) during dark phase. These results are discussed in light of complex opiate-oxytocin/vasopressin interactions in the regulation of food intake.

Estrogen actions on brain and behavior: recent insights and future challenges.

Recent advances in our knowledge of estrogen action in the brain suggest that this steroid is not solely an endocrine factor but plays important but hitherto largely unrecognized physiological and pathophysiological roles that are not directly involved in reproductive processes. Estrogens are now known to influence a wide variety of functions in the mammalian brain ranging from regulation of various aspects of neurotransmitter function and modulation of behaviour to the stimulation of differentiation and plasticity of distinct neuronal populations and circuits. Acting via both genomic and nongenomic mechanisms estrogens can influence higher cognitive functions, pain mechanisms, fine motor skills, mood, susceptibility to. seizures, and also appear to have important neuroprotective function in relation to stroke damage and neurodegenerative disorders. This review focuses on new advancements from clinical and basic studies on estrogen action in the central nervous system especially illustrating the brain regions and cell types in which estrogens produce their effects, emphasizing new knowledge regarding estrogen actions outside the hypothalamus and pituitary gland. Current therapeutic strategies to develop suitable estrogen receptor modulators with a selective spectrum of action in the brain and priorities for future research are also briefly discussed.

Role of diurnal variation and receptor specificity in the opioidergic regulation of food intake in free-fed and food-deprived rats

The effects of opioid agonists, morphine (MOR) and ketocyclazocine (KCZ), and antagonists, naltrexone (NALTX) and Mr2266, were investigated on food intake under various conditions, i.e., during light and dark phases of diurnal cycle and free-fed and fasting states in rats. NALTX showed a greater anorexic effect during dark phase, whereas Mr2266 produced such effect during light phase. This suggests that mu-receptors play a major role during dark phase while kappa-receptors are more important in light phase. The comparison of effects of different opioidergic drugs in fasted and free-fed rats showed that NALTX and Mr2266 reduced the elevated basal food intake in 18-h fasted rats to free-fed control levels. Therefore, it appears that enhanced endogenous mu- and kappa-directed neural mechanisms are one of the factors responsible for enhancing food intake in fasted rats. Differential role of MOR and KCZ on food intake in free-fed and fasted rats is also indicated in our study. Both agonists produced a biphasic response in fasted rats, i.e., hyperphagia (0-1 h) followed by hypophagia (1-6 h). However, a generalized hyperphagic effect is observed in free-fed rats (except during 3-6 h by MOR). The initial hyperphagic effect is more prominent in fasted rats which may be due to additive effects of endopioid mechanisms. Specificity of the response at various intervals is confirmed by blockade with NALTX and Mr2266. NALTX appears more potent than Mr2266 in antagonising the effects of MOR but markedly less potent than Mr2266 in inhibiting the effects of KCZ. This suggests that both MOR and KCZ have a mu as well as kappa component in food intake response.

Differential effects of intrahypothalamic administration of opioids on food intake in naive and tolerant rats.

We investigated the effects of intrahypothalamic administrations of the opioid agonists morphine (MOR) and ketocyclazocine (KCZ) and antagonists naltrexone (NALTX) and Mr2266 on food intake (FI) during light and dark phases of the diurnal cycle, after acute or chronic administration in rats. Acute intralateral hypothalamic (LH) administration of MOR or KCZ (1 microgram/rat) enhanced FI during dark and light phases, respectively, whereas intraventromedial hypothalamic (VMH) injections resulted in moderate hyperphagia during dark phases by both mu and kappa agonists. The receptor specificity was evident from blockade of the responses to MOR or KCZ by the respective antagonists NALTX and Mr2266. After repeated administrations of MOR and KCZ, FI responses to the test dose of these agonists injected in LH were modulated in opposite directions. However, the adaptative changes in FI after intra-VMH injection of KCZ were similar to those seen with MOR. These results are discussed in light of a differential opioid receptor involvement and their possible functional interactions within the hypothalamus during food intake.

Effects of intrahypothalamic morphine and its interactions with oxytocin and vasopressin during food intake in rats

The effects of intra-hypothalamic microinjections of morphine (MOR) into the ventromedial (VMH) and lateral (LH) nucleus and its interactions with oxytocin (OXY) and vasopressin (AVP) were evaluated during food intake FI) in rats. Acute MOR clearly enhanced FI during the dark phase (6-24 h) of the diurnal cycle, while no appreciable changes in the light phase (0-6 h) FI was seen after intra-VMH or LH injections. Long term MOR administration into both VMH and LH attenuated the enhancements in FI seen after acute MOR during the dark phase, while FI was enhanced during the light phase. Pretreatment with OXY or AVP clearly antagonized such tolerance or reverse tolerance/sensitization development to the orexic effect of MOR. These results are discussed in the light of complex peptidergic interactions in the hypothalamus during ingestive behavior.

Stress: its impact on reproductive and developmental toxicity

Publisher Summary This chapter summarizes stress and its impact on reproductive and developmental toxicity. It describes the impact of prenatal stress experienced by the mother on development of the fetus during pregnancy and later in postnatal life. The four broad categories of stressors are explained here. Regarding the origins of individual differences, two kinds of models have been suggested. Multiple brain structures are involved in the organization of responses to aversive or stressful stimuli. The role of the neuroendocrine axis during fetal development is explained with appropriate research findings. It summarizes the prenatal stress and its impact on fetal growth and on later life. The influence of stress on reproduction results from interactions between endocrine, paracrine and neural systems, which are also discussed. There are important trade-offs between immediate survival in the developmental habitat vs. long-term phenotypic changes that result in reduced performance as an adult. These neuroendocrine/developmental responses, and their long-term phenotypic consequences, are deeply rooted in the evolutionary history of vertebrate animals. The effects of maternal psychosocial processes are mediated, in part, by the maternal–placental–fetal neuroendocrine axis. The psychoneuroendocrine processes may interact with immune processes to influence the risk of reproductive tract infection and its pathophysiological consequences.

Pharmacological and biochemical studies on the protective effects of melatonin during stress-induced behavioral and immunological changes in relation to oxidative stress in rats.

Stress is known to precipitate neuropsychiatric diseases, and depending upon its nature and intensity it can also influence the functioning of the immune system. Melatonin (N-acetyl-5-methoxy tryptamine) a pineal gland hormone and potent antioxidant is known to protect against many diseases. Effect of melatonin in stress-induced neuro-immunomodulation is not well elucidated. Therefore in the present study, the protective effects of melatonin were evaluated in restraint stress (RS)-induced behavioral and immunological changes in rats. RS for 1 h significantly reduces (i) percentage of open-arm entries and (ii) percentage of time spent on open-arm in elevated plus maze (EPM) test parameters (p < 0.01) and significant increase in MDA levels in brain homogenate when compared to non-RS control groups (p < 0.05). In immunological studies, both humoral and cell-mediated immune responses to antigen were significantly suppressed by RS for 1 h for 5 consecutive days, as evidenced by significant reduction in (i) anti-SRBC antibody titre, (ii) PFC counts, (iii) percentage change in paw volume, and (iv) Th1 (IFN-γ) and Th2 (IL-4) cytokine levels (p < 0.001 in all parameters). These RS-induced immunological changes were associated with significantly increased lipid peroxidation (MDA) levels in serum and significantly decreased activity of (i) SOD, (ii) CAT, and (iii) GSH levels in RS (X5)-exposed group (p < 0.02). Pretreatment with melatonin (10, 50, and 100 mg/kg) significantly reversed these RS-induced changes in EPM test parameters and humoral and cell-mediated immunological parameters, as well as oxidative stress markers in a dose-dependent manner by differential degrees (p < 0.001). Results are strongly suggestive of the involvement of free radicals during stress-induced neurobehavioral and immunological changes. These changes were significantly restored by melatonin pretreatment. We can conclude that melatonin may have a protective role during such stress-induced neuro-immunomodulation.

Nutraceuticals as Adaptogens: Their Role in Health and Disease

Abstract Stress is any physical, psychological, and/or environmental stimulus capable of altering physiological homeostasis, and the ability to cope with such stressful stimuli is a crucial determinant of health and disease. Several aggressive and defensive factors are involved in the organization of a stress response, and maintenance of a balance results from an interaction between complex neurochemical pathways. Conventional antistress agents like benzodiazepines, although effective, have a plethora of undesirable effects that restricts their long-term use, and thus there is a constant search for more effective and safer agents. Nutraceuticals are food additives and/or nutritional supplements used for the prevention and treatment of many diseases as well as for maintenance of normal well-being. Some such nutraceuticals known as adaptogens primarily obtained from herbal sources (medicinal plants) act as antistress agents and, in recent years, have gained considerable attention because of their safety, efficacy, and cost-effectiveness. Experimental and clinical studies have validated their uses, and much scientific research has clarified their efficacy and safety issues in human diseases. In view of this and the increasing awareness of the population about lifestyle disorders, the use of such nutraceuticals may revolutionize the management of some of these debilitating disease states. It is suggested that due to their antistress effects, adaptogens could not only help to counteract stress effects on the biological system but also increase nonspecific resistance to a variety of other aversive stimuli. This, in turn, could be helpful in protecting against stress-related diseases and in improving the quality of life.

Role of the paraventricular nucleus in the reflex diuresis to pulmonary lymphatic obstruction in rabbits

The changes in urine flow and renal sympathetic nerve activity (RSNA) due to pulmonary lymphatic obstruction (PLO) were examined in anesthetized, artificially ventilated New Zealand white rabbits. PLO was produced by pressurizing an isolated pouch created in the right external jugular vein at the points of entry of the right lymphatic ducts. During this maneuver, urine flow increased from 8.5 ± 0.3 mL/10 min to 12 ± 0.5 mL/10 min (P < 0.0001) and RSNA increased from 24.0 ± 4 to 40.0 ± 5 μV·s (P < 0.0001). Bilateral lesioning of the paraventricular nucleus (PVN) of the hypothalamus or cervical vagotomy abolished these responses. PLO increased c-fos gene expression in the PVN. The increase in urine flow due to PLO was attenuated by muscimol and abolished by kynurenic acid microinjections into the PVN. The results show that (i) neurons in the PVN are an important relay site in the reflex arc, which is activated by PLO; and (ii) this activation is regulated by glutamatergic and partly by GABAergic input to the PVN.