Velayudhan Mohan Kumar

Inhibition of male sexual behavior by serotonin application in the medial preoptic area

The study investigated the possible involvement of serotonin in the medial preoptic area in the regulation of sexual behavior of male rats. Injection of serotonin in the medial preoptic area resulted in an inhibition, whereas cyproheptadine (a serotonin antagonist) produced a slight facilitation, of male sexual behavior.

Orexin A (hypocretin-1) application at the medial preoptic area potentiates male sexual behavior in rats.

The medial preoptic area plays an important role in the regulation of male sexual behavior in rats, and this area receives orexinergic inputs. The role of orexinergic inputs in the medial preoptic area in sexual behavior has not been studied, though they have been shown to play a role in some other physiological functions. In this study, the changes in male sexual behavior in rats were studied after local injection of orexin A (Hypocretin-1) at the medial preoptic area. The results of the study showed that orexin A application at the medial preoptic area increased sexual arousal as well as the copulatory performance. Sexual arousal is one of the physiological stimuli, which influences wakefulness. It is possible that the earlier reports showing increased wakefulness, on application of orexin A at the medial preoptic area/basal forebrain, has a contribution from sexual arousal.

Noradrenergic afferents and receptors in the medial preoptic area: neuroanatomical and neurochemical links between the regulation of sleep and body temperature.

Several studies have shown the importance of the medial preoptic area in the regulation of sleep-wakefulness and of body temperature. The medial preoptic area has a rich noradrenergic innervation, coming mostly from the lateral tegmental noradrenergic system. The accumulating evidences show that the noradrenergic afferents to the medial preoptic area are involved in the induction of sleep. This hypnogenic mechanism operates through the postsynaptic alpha1 and alpha2-adrenergic receptors. Noradrenergic afferents are also involved in the thermoregulatory mechanisms, and the activation of these fibers brings about a fall in body temperature. Though the body temperature changes are brought about by the same receptor subtypes as those involved in hypnogenesis, observations suggest the possibility of separate sets of noradrenergic afferents in the medial preoptic area for sleep regulation and thermoregulation. In this review, we present the compelling evidences, which showed that the noradrenergic afferents of the medial preoptic area bring about a fall in body temperature and other thermoregulatory behavioral alterations associated with sleep.

The role of alpha-2 receptors in the medial preoptic area in the regulation of sleep-wakefulness and body temperature.

The study was conducted on 48 free-moving male rats to find out the role of the medial preoptic alpha2 receptors in the regulation of sleep and body temperature. Recording electrodes for assessment of sleep-wakefulness, and injector cannulae for injection of drugs in the medial preoptic area were chronically fixed on the skulls of the animals. The noradrenergic fibres projecting to the medial preoptic area were destroyed in 24 rats by administration of 6-hydroxydopamine at the ventral noradrenergic bundle. Though arousal was produced in normal rats by the injection of the alpha2 adrenergic agonist, clonidine, at the medial preoptic area, it induced sedation in rats with noradrenergic fibre lesion. Clonidine did not alter the rectal temperature in normal rats but it induced hypothermia in lesioned rats. Injection of alpha2 antagonist, yohimbine, at the medial preoptic area induced sleep in rats with intact noradrenergic fibres. However, the sleep inducing effect of this drug was very much attenuated in the lesioned animals. There was no significant change in body temperature, in both these groups of animals, after yohimbine administration. The study indicates the role of presynaptic alpha2 adrenergic receptors in arousal response and indirectly supports the contention that the alpha1 postsynaptic receptors at the medial preoptic area are involved in hypnogenesis. It also suggests that the thermal changes induced by adrenergic system are mediated through alpha1 postsynaptic receptors. But the thermal changes do not contribute towards the induced alterations in sleep-wakefulness. It is proposed that there should be separate sets of noradrenergic terminals for regulation of sleep and body temperature.

Alpha adrenergic system in medial preoptic area involved in sleep-wakefulness in rats

The study is aimed at investigating the possible involvement of adrenergic mechanisms in the medial preoptic area (mPOA) for modulation of sleep-wakefulness in rats. In this study, saline, norepinephrine (NE), phenoxybenzamine (PBZ) and propranolol (PROP) were injected in the mPOA in different groups of male rats during the day and night. NE and PBZ were injected, during the day and the night respectively, in some control areas adjoining the mPOA in two other groups of animals. Arousal was produced by NE, and sleep by PBZ when they were applied in the mPOA. All other procedures, including application of NE and PBZ in the control areas and beta blocker (PROP) in the mPOA, did not produce alterations in sleep-wakefulness. These findings provide support for a physiological role played by the alpha adrenergic system in the mPOA for arousal, and area specificity of action of this system.

Role of medial preoptic area beta adrenoceptors in the regulation of sleep-wakefulness

The role of the medial preoptic area (mPOA) beta adrenergic receptors in the regulation of sleep-wakefulness (S-W) was investigated in this study. S-W was assessed on the basis of polygraphic recording of EEG, EMG and EOG in free moving rats. Intracerebral microinjection of beta agonist, isoproterenol, into the mPOA produced arousal. The study was also conducted on another set of rats in which noradrenergic (NE) innervation to the mPOA was destroyed by injecting 6-hydroxydopamine into the ventral noradrenergic bundle, in the brain stem. Local application of isoproterenol, into the mPOA, in these animals, did not produce any significant change in S-W. Thus, the increase in awake period obtained on isoproterenol administration was the result of its action on the presynaptic NE terminals. Possible involvement of other responses in the isoproterenol induced increase in wakefulness, is discussed.

Differences in the effects of medial and lateral preoptic lesions on thermoregulation and sleep in rats

The effects of the destruction of the medial preoptic area and the lateral preoptic area with N-methyl-d-aspartic acid on sleep-wakefulness, brain temperature and thermoregulation were studied in two groups of male Wistar rats. Electroencephalogram, electrooculogram and electromyogram, along with brain temperature, were recorded for 3 days, prior to the destruction of the medial preoptic area and the lateral preoptic area, and on the 7th and 21st days after the destruction of these areas. The thermoregulatory capacity of the rats was assessed by recording their brain temperature when they were exposed to severe cold (5+/-1 degrees C) and heat (37+/-1 degrees C) before and after the lesion. Though sleep was decreased after the destruction of both the medial preoptic area and the lateral preoptic area, paradoxical sleep was reduced only by the destruction of the medial preoptic area. Decrease in sleep after the medial preoptic area lesion was brought about by a decrease in the duration of the slow wave sleep episodes and the frequency of paradoxical sleep episodes. Decrease in sleep after the lateral preoptic area lesion was brought about by a decrease in the frequency of slow wave sleep episodes. There was a significant increase in brain temperature after the medial preoptic area lesion but not after the lateral preoptic area lesion. The rats with lesion in the medial preoptic area showed deficits in thermoregulation on exposure to cold, while those with the lateral preoptic area lesion showed deficits in heat defense ability. The present findings suggest that the medial preoptic area and the lateral preoptic area regulate sleep by different modalities and that there is an anatomical segregation of heat and cold defense functions within the basal forebrain.

Changes in thermal preference, sleep-wakefulness, body temperature and locomotor activity of rats during continuous recording for 24 hours

This study was aimed at correlating diurnal changes in thermal preference of rats with their body temperature (Tb), sleep-wakefulness (S-W) and locomotor activity (LMA). Electroencephalogram (EEG), electromyogram (EMG), electrooculogram (EOG) and Tb were recorded by telemetry, while an activity monitor measured LMA and thermal preference. A special environmental chamber, which was designed and fabricated, enabled for the first time, simultaneous measurement of thermal preference, along with S-W and Tb. S-W, thermal preference and LMA were recorded continuously in six adult male Wistar rats, for 24 h, for 3 days, and Tb with thermal preference and LMA were recorded for another 3 days. LMA and Tb were higher at night than during day. The rats slept less during the night time. Increased frequency of sleep episodes contributed towards increased sleep during day time. They preferred an ambient temperature (Tamb) of 24 degrees C at night and 27 degrees C during the day. Though the preference for higher Tamb during day time coincided with increased sleep, the rats did not move over to higher Tamb prior to the onset of sleep episodes. Though the diurnal alterations in sleep, Tb and LMA were similar to those reports from animals kept in constant Tamb, the day-night variation of paradoxical sleep (PS) was exaggerated when the rats selected their own preferred Tamb.

Role of the lateral septal noradrenergic system in the elaboration of male sexual behavior in rats.

The study was aimed at investigating the possible involvement of noradrenergic mechanisms in the lateral septum (LS) for elaboration of male sexual behavior in rats. In this study, norepinephrine (NE), yohimbine (YOH), isoproterenol (ISOP), propranolol (PROP), saline (SAL) and dimethyl sulfoxide (DMSO) were injected bilaterally in the LS in six different groups of sexually active male rats, and various components of sex behavior were recorded. The application of NE (3 microg) and alpha(2)-antagonist YOH (1 microg) produced a stimulation of most of the components of male sexual behavior, and there was increase in sexual arousal as well as performance. The microinfusion of nonspecific beta-agonist ISOP (2 microg) also produced a stimulation of copulatory behavior whereas beta-antagonist PROP (2 microg) produced an inhibition. The stimulation of male sexual behavior by YOH application at the LS could be due to an increased release of NE by its blocking effect on presynaptic alpha(2)-receptors. These results suggest that the noradrenergic system in the LS has stimulatory effect upon male sexual behavior, probably acting through beta-receptors.

Medial preoptic alpha-2 adrenoceptors in the regulation of sleep-wakefulness

Adrenergic alpha 2 agonist (clonidine) and its antagonist (yohimbine) were locally applied to the medial preoptic area (mPOA), to find out the role of alpha 2 receptors at this brain region in the regulation of sleep-wakefulness. Clonidine produced arousal, whereas yohimbine induced sleep in freely moving animals. Behavioural arousal produced by clonidine administration was accompanied by EEG synchronization. The alpha 2 receptor as the probable site of action of externally applied norepinephrine (NE), is discussed.