Changes in succinate dehydrogenase activity of rats after intraventricular injections of GABA, muscimol and picrotoxin.

Effects of intraventricular injections of GABA, and a GABA agonist, muscimol and an antagonist, picrotoxin on succinate dehydrogenase (SDH) enzyme activity in plasma and a few hypothalamic nuclei of brain of rats have been investigated using biochemical, histochemical and cytophotometric techniques. Results show that SDH decreased by GABA and muscimol treatment, and increased after picrotoxin injection. From the above findings, it is apparent that GABA, muscimol and picrotoxin influence SDH activity of plasma and hypothalamic nuclei.

Electrical activity and feeding correlates of intracranial hypothalamic injection of GABA, muscimol and picrotoxin in the rats.

Assemblies of electrodes and a cannula were stereotaxically implanted in the ventromedial (VMH), lateral (LHA) and paraventricular (PVH) hypothalamic areas in male albino rats. Electrical activity of these regions was recorded electrographically before and following intracranial injection (ICI) of GABA, muscimol and picrotoxin. In another set of animals, food intake and water intake were also measured. The activity of the ventromedial hypothalamus changed from slow to fast after ICI of GABA and picrotoxin and fast to slow after muscimol. The activity of the lateral hypothalamus changed from slow to fast with ICI of muscimol and picrotoxin and from fast to slow with GABA, while that of the paraventricular hypothalamic nucleus changed from slow to fast with ICI GABA and fast to slow with muscimol and picrotoxin. ICI of GABA into VMH and LHA and muscimol in VMH, LHA and PVH caused a decrease in food intake. Water intake was also decreased after ICI of GABA in PVH and muscimol in LHA and PVH. On the opposite picrotoxin increased food intake in VMA and LHA and water intake in PVH. The possible interaction of GABAergic drugs with the areas of the brain controlling feeding and drinking is being discussed.

Butyrylcholinesterase fluctuation in male albino rats with intracerebroventricular injection of gamma aminobutyric acid, muscimol, and picrotoxin.

The effects of intracerebroventricular injection of gamma-Aminobutyric acid, muscimol, or picrotoxin have been studied on butyrylcholinesterase (BuChE) activities in the serum and several hypothalamic nuclei using biochemical, histochemical, and cytophotometric techniques, respectively. The blood samples were withdrawn from indwelling catheters in jugular vein 1, 15, 30, 45, 60, 90, and 120 min after injection of the drugs. Biochemical estimations demonstrated a significant inhibition of BuChE after GABA and muscimol injections, whereas a pronounced stimulation of BuChE was observed after injection of picrotoxin. The peak changes were observed within 30 min of drug injection. Cytophotometric studies have appeared to dovetail the biochemical findings. Only a marginal decrease was observed after injection of GABA in all nuclei, while muscimol induced a very conspicuous decrease of BuChE. On the contrary, intracerebroventricularly administered picrotoxin markedly increased the levels of BuChE activity. Thus it could be concluded that probably GABA and muscimol along with picrotoxin appear to alter BuChE.

Effect of GABA, muscimol and picrotoxin given in third ventricle on serum cholinesterases and monoamine oxidase and on plasma succinic dehydrogenase in rats.

Effect of injection in third ventricle of GABA, the GABA agonist muscimol, and the GABA antagonist picrotoxin on the activities of acetylcholinesterase (AChE), butyrylcholinesterase (BuChE) and monoamine oxidase (MAO) in serum and succinic dehydrogenase (SDH) in plasma has been studied. Surprisingly, the AChE, BuChE, MAO and SDH enzymes activity were inhibited by GABA and muscimol, while they were enhanced by picrotoxin.

Effect of GABA muscimol and picrotoxin on electrical activity of the medial preoptic area in unanesthetized rats.

Intracranial cannula along with electrodes was stereotaxically implanted in medial preoptic area of male rats. The electrical activity of mPOA was recorded before and after microinjection of GABA (0.5 micrograms/02 microliters), muscimol (0.5 micrograms/0.2 microliter), picrotoxin (0.25 micrograms/0.2 microliter) and their respective controls. Generalized slowing with an increase in amplitude appeared with GABA and muscimol, while picrotoxin produced just the reverse, i.e. fast activity. Thus the mPOA seems to be vulnerable to GABAergic compounds and supports the diversity of physiological and behavioral functions.

Centrally administered GABA and GABA-selective agonist and antagonist in rats: histoenzymological cytophotometric study.

In the present study, the effect of intracerebroventricular (icv) injection of GABA, its agonist--muscimol, and antagonist--picrotoxin, has been studied on histoenzymological alterations of acetylcholinesterase (AChE). butyrylcholinesterase (BuChE), monoamine oxidase (MAO), and succinic dehydrogenase (SDH) by cytophotometric technique. This study was conducted on medial preoptic area (mPOA), nucleus paraventricularis hypothalami (PVH), area lateralis hypothalami (LHA), nucleus dorsomedialis hypothalami (DMH), and nucleus ventromedialis hypothalami (VMH). Results showed that GABA and muscimol inhibited AChE, BuChE, MAO, and SDH in all the areas while picrotoxin stimulated these enzymes. These changes in enzyme activity by GABA, muscimol, and picrotoxin and their possible mode of action are discussed.

Qualitative and quantitative changes in monoamine oxidase activity after acute third ventricle treatment of GABA, muscimol, and picrotoxin in rat.

The effect of acute IIIrd ventricle injection of GABA, muscimol, and picrotoxin on the activity of monoamine oxidase (MAO) has been investigated in serum and a few hypothalamic nuclei of the rat brain using biochemical, histochemical, and cytophotometric techniques. Biochemical estimation demonstrated a significant reduction in MAO enzyme activity after GABA and muscimol injection, whereas picrotoxin produced pronounced increase in the enzyme activity. Histochemical and cytophotometric studies confirmed the biochemical findings. Even in brain, GABA and muscimol inhibited and picrotoxin stimulated the MAO activity. From the above findings, it may be concluded that GABA, muscimol, and picrotoxin regulate the MAO activity, possible mechanisms for which are being discussed.

Effect of third ventricle injection of GABA to feeding responses and blood sugar in intact and ovariectomized female rats.

Injections into third ventricle of brain of either 4 m Molar or 8 m Molar of GABA were given to intact and ovariectomized female rats to evaluate the effects of these dosages on body weight, food intake, water intake and blood glucose levels. Statistically significant reduction in food and water intake with 8 m Molar GABA was observed in intact female rats. Very precise alterations seen in ovariectomized female rats suggested that GABA could demonstrate more profound effects on body weight, food intake and water intake. Blood glucose level was elevated in both the groups with 4 m Molar GABA, while inhibition was seen with 8 m Molar GABA. These observations have been correlated with trophic hormonal profiles, which are modulated by third ventricle GABA injection or it might have had some intervention on hypothalamic mechanisms regulating these functions.

Effect of chronic intracerebroventricular morphine to feeding responses in male rats.

Stainless steel cannulae were implanted stereotaxically in the third ventricle of male albino rats. The rats were fed with natural food pellets and water ad lib. After seven days of cannulation, daily body weight, food intake and water intake were recorded for the first five days, which was considered the preinjection control. Then increased and repetitive injections of morphine sulphate were administered intracerebroventricularly (ICV) in dosage of 30 micrograms/2 microliter, 45 micrograms/3 microliter, 60 micrograms/4 microliter, 75 micrograms/5 microliter, 90 micrograms/6 microliter and 105 micrograms/7 microliter on each following day respectively. In a separate set of experiments, the blood glucose levels were measured in animals injected with morphine to a dose corresponding to 15 micrograms/1 microliter, 30 micrograms/2 microliter, 45 micrograms/3 microliter, 60 micrograms/4 microliter and 75 micrograms/5 microliter on days 1, 2, 3, 4 and 5 respectively. Statistically significant (p less than 0.001) decreases in the body weight, food intake, water intake and increase in blood glucose were observed. The inferences derived from the above observations for the possible involvement and interaction of opioids in the regulation of feeding mechanisms have been discussed.

Cumulative effect of prostaglandin E2(PGE2) injections on electroencephalographic activity in male monkeys (Macaca mulatta).

Bipolar stainless steel electrodes were stereotaxically implanted in hypothalamic and cerebral cortical regions of 24 adult male gonadally intact monkeys. Electrical activity of these regions was recorded before and after the first, second, third, thirteenth, fourteenth and fifteenth day of intravenous (I. V.) injection of PGE2 (400 mikrogramm/kg body weight). The inferences drawn from the EEG record were: (i), the immediate response was a tendency towards spindle formation (ii), high voltage spindles appeared at regular intervals in all sites i.e., preoptic area, posterior hypothalamus, ventromedial nucleus and cerebral cortex (iii), the changes observed. in EEG were progressive with time and transitional with respect to various regions of the brain (iv), these changes were synchronized whenever and wherever they were present, but the generalized showing in the form of overall inhibition could never be seen (v), the dose showed a cumulative effect after repeated daily injections of PGE2.

Acute inhibition of PRL and TSH secretion after intraventricular injection of PRL in ovariectomized rats.

Prolactin (PRL) is under short-loop inhibitory control via the hypothalamus. However, earlier studies evaluated the effects on PRL secretion of PRL levels elevated for periods of days. In this study we evaluated the acute effects of intraventricular and systemic injection of PRL on the release of a variety of pituitary hormones. Ovariectomized (OVX) rats, bearing implanted third ventricular and jugular cannulas were used. Blood was withdrawn in unanesthetized, freely moving animals before and after intraventricular injection of 0.9% NaCl or 1 or 3 micrograms of bovine (b) or ovine (o) PRL. Prolactin was also administered intravenously in doses of 3 or 6 micrograms. No effect on plasma levels of any of the pituitary hormones occurred after intraventricular or systemic injection of saline. Intraventricular injection of both doses of bPRL or oPRL significantly lowered plasma PRL within 15-30 min. In animals with elevated initial PRL values because of stress or estradiol (E) priming, greater lowering of PRL occurred. Inconsistent reductions in plasma PRL occurred after intravenous injection of oPRL but not bPRL, which elevated PRL values via cross-reaction in the immunoassay. In contrast, only small and inconsistent declines in luteinizing hormone (LH) were seen after intraventricular injection of PRL in either OVX or OVX E-primed rats. Plasma follicle-stimulating hormone (FSH) and growth hormone (GH) were not affected by PRL in any of the experiments; however, a significant lowering of thyrotropin (TSH) occurred in OVX or OVX E-primed rats within 30 min after intravenous injection of 3 micrograms of oPRL, but no change occurred after intravenous PRL. The data indicate that PRL can acutely inhibit PRL and TSH release via a hypothalamic action, whereas release of LH is only slightly inhibited and that of FSH and GH is unaltered.

Possible effects of prostaglandin (PGE2) on hypothalamo-hypophyseal-gonadal axis in male rhesus monkeys (Macaca mulatta).

The effect of hypothalamo-hypophyseal-gonadal axis of prostaglandin E2 (PGE2) administered in a dose of 500 micrograms/kg body weight/day for 15 days to adult monkeys is reported. It altered the functional integrity of the testis and accessory sex organs as reflected by the changes in the estimations of the alkaline phosphatase, acid phosphatase, succinic dehydrogenase in the testis, sialic acids in caput and cauda epididymis, citric acid in the seminal vesicles, and fructose in the prostate and seminal vesicles. Histologically, PGE2 produced a marked decrease in the sperm count and an increase in the number of and size of exfoliated granulocytes was observed, which might have been due to the stimulatory effect of PGE2 on gonadotrophin release. The alterations induced in the electroencephalograph also suggest an involvement of hypothalamic mechanisms for gonadotrophin release, for which certain plausible explanations have been provided. The results suggest that the changes in reproductive parameters might be a consequence of endocrinological and functional disturbance induced by PGE2 and there is a strong likelihood of involvement of hypothalamo-pituitary integration in this complex.

Mapping of evoked responses from different areas of hypothalamus on stimulation of spermatic nerve in monkeys.

Stainless steel pedestal was implanted on the skull of 12 adult anesthetized rhesus monkeys, according to the predetermined stereotaxic coordinates of hypothalamus. For recording, conscious monkey was made to sit on its chair in a shielded cage to minimize interfering artifacts. Spermatic nerves were stimulated with concentric needle electrodes inserted into undissected portion of the spermatic cord and evoked responses were recorded from a number of hypothalamic areas. Responses with initial negative and positive phases appeared in the anteromedial and posterior hypothalamic regions respectively. The middle medial portions of hypothalamus showed non-conductive local activity, while the lateral regions at the same anteroposterior co-ordinates gave responses, which showed a positive negative response more on a pattern of primary sensory motor cortex. The results indicate smaller latency zones in medial part and longer latency in anterior and posterior parts, and suggest that hypothalamic excitation occurs via periventricular fiber system.

Antiandrogenic effects of cyproterone acetate and chloromadinone acetate on the rat hypothalamus as revealed by electroencephalographic responses.

Bipolar stainless steel electrodes were implanted stereotaxically into given hypothalamic and cortical regions of the brain of 48 rats. The animals were divided into two groups of equal numbers and the electrical activity of the given regions was recorded electroencephalographically (EEG). The effect of the acute and chronic administration of cyproterone acetate (CPA) or chloromadinone acetate (CHA), in doses inducing sterility, on EEG activity were observed. Apart from slight inhibition in the preoptic region, no appreciable EEG changes were found after CPA, while CHA reduced the discharge frequency in both the preoptic and the posterior hypothalamus. These findings can be attributed to the presence of two different types of androgen receptors in the hypothalamus.

Effects of estradiol dipropionate on the biochemical composition of testis and accessory sex organs of adult rats.

A short term treatment of 14 days with estradiol dipropionate, ovocyclin¿ to adult male albino rats for 7 and 14 days in a dose of 2 mg/rat significantly inhibited the structural and functional integrity of the testis and accessory glands. The weights of these organs were significantly reduced. The activity of the enzymes acid and alkaline phosphatase and succinic dehydrogenase in testis and the concentration of sialic acids, fructose and citric acid in caput and cauda epididymides, prostate and seminal vesicles respectively were significantly lowered after both treatments. All these changes were found to be irreversible even on withdrawal of ovocyclin¿ for 28 days after 14 days treatment. On discussing the results with previous reports, it is proposed that estrogens probably impede the activity of these organs by inhibition of androgen production, their antiandrogenic nature or their direct action on these organs.