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Biomedical subjects

A Gulati

Publications and source records attributed to A Gulati.

At least 109 records · Page 6Linked to original sources
PubMed1990

Hypertension and myocarditis in rabbits exposed to hexachlorocyclohexane and endosulfan.

Male albino rabbits were exposed to the organochlorinated pesticides hexachlorocyclohexane (HCH) and endosulfan (2.5 and 5.0 mg/kg, ip) twice a week for 12 mo. The mean body weight of the rabbits at 12 mo was lower than that of the controls. There was rise in blood pressure and heart rate. Electrocardiograms (ECG) in both the exposed groups showed increases in PR, QT and RR intervals. Extensive myocardial damage was recorded with marked degeneration of muscle fibers vacuolization and leucocytic infiltration. Adrenals had thickened capsules and hyperplasia of cortical cells. Both pesticides produced significant increases (p less than 0.001) of 11-hydroxycortisone at all time intervals. Hypertension and myocarditis occurred in rabbits exposed to HCH and endosulfan.

Adrenal Glands↗
PubMed1990

Modification of brain and spinal cord dopamine D1 receptors labeled with [3H]SCH 23390 after morphine withdrawal from tolerant and physically dependent rats.

The effect of morphine tolerance-dependence and abstinence on dopamine D1 receptors in brain regions and spinal cord was determined in rats. Male Sprague-Dawley rats were implanted s.c. under light ether anesthesia with 6 morphine pellets, each containing 75 mg of morphine free base. Rats serving as controls were implanted with placebo pellets. This procedure resulted in the development of tolerance to morphine as evidenced by decreased analgesic response to a challenge dose of morphine. Similarly, the development of physical dependence was evidenced by decreased body weight and colonic temperature after morphine pellet removal (withdrawal). Two sets of animals were used for receptor binding studies. In one, the pellets were left intact and in the other, the pellets were removed. Eighteen hours after pellet removal, the rats were sacrificed. [3H]SCH 23390 [( R-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1-3-benzapine- 7-ol]) bound to brain region and spinal cord membranes of placebo pellet-implanted rats at a single high affinity site. In rats treated chronically with morphine and then withdrawn, the binding of [3H]SCH 23390 to membranes of spinal cord, hypothalamus and striatum was increased but the binding to amygdalar membranes was decreased in comparison with placebo-treated rats. The changes in binding were due to the changes in Bmax values; the Kd values were unaffected. The behavioral responses to a selective dopamine D1 receptor agonist, SKF 38393 [( 1-phenyl-2,3,4,5-tetrahydro (1H)-3-benzapine-7,8-diol hydrochloride]), were also enhanced in morphine-withdrawn rats when compared to placebo controls.(ABSTRACT TRUNCATED AT 250 WORDS)

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1989

Brain and spinal cord 5-HT2 receptors of morphine-tolerant-dependent and -abstinent rats.

The effects of morphine tolerance-dependence and abstinence on 5-HT2 receptors in brain and spinal cord of the rat were determined. Tolerance to and physical dependence on morphine was induced in male Sprague-Dawley rats by implanting six morphine pellets (each containing 75 mg of morphine free base) during a seven day period. Two groups of rats were used for binding studies. In one group the pellets were left intact and in the other they were removed. The rats were killed and spinal cords and brains were excised and dissected into six regions (amygdala, hippocampus, hypothalamus, striatum, midbrain and pons + medulla). 5-HT2 receptors were characterized by using [3H]spiperone as the ligand and unlabelled ketanserin to determine the non-specific binding. In morphine and placebo abstinent rats the binding of [3H]spiperone to 5-HT2 receptors in brain regions and spinal cord did not differ. The Bmax values of [3H]spiperone to bind to membranes prepared from non-abstinent morphine-dependent rats were increased in amygdala (78.0%), midbrain (65.0%) and pons + medulla (92.0%). The Kd values were unaffected. It is concluded that in morphine-tolerant-dependent rats 5-HT2 receptors are up-regulated in amygdala, midbrain and pons + medulla, but in morphine-abstinent rats they are unaffected.

Animals↗
PubMed1989

Effects of morphine in rats treated chronically with U-50,488 H, a kappa opioid receptor agonist.

The pharmacological effects of morphine, namely analgesic, hyperthermic and cataleptic effects, were assessed in rats rendered tolerant to U-50,488H, a kappa opioid receptor agonist. Male Sprague-Dawley rats were injected intraperitoneally with U-50,488H (25 mg/kg) twice a day for four days. The rats which served as controls were injected similarly with the vehicle. Chronic administration of U-50,488H resulted in the development of tolerance to its analgesic and hypothermic effects, but not to its diuretic effect. The development of tolerance to the pharmacological effects of U-50,488H was associated with decreased binding of [3H]ethylketocyclazocine [( 3H]EKC) to brain and spinal cord membranes. The decreased binding of [3H]EKC in U-50,488H-treated rats was due to changes in the Bmax value; the Kd values remained unaltered. Intraperitoneal administration of morphine (8 mg/kg) to rats produced analgesia (as determined by the tail-flick test) and hyperthermia. A dose of 50 mg/kg of morphine produced cataleptic response. The intensity of analgesic, hyperthermic and cataleptic effects of morphine were unaltered in rats tolerant to U-50,488H. The development of tolerance to analgesic and hypothermic effects of U-50,488H were associated with down-regulation of brain and spinal cord kappa opioid receptors. Finally, U-50,488H does not confer cross-tolerance to morphine, a predominantly mu opioid receptor agonist.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1989

Methionine-enkephalin and beta-endorphin levels in spleen and thymus gland of morphine tolerant-dependent and abstinent rats.

The effect of chronic administration of morphine and abrupt and naloxone-precipitated withdrawal on the levels of beta-endorphin and methionine-enkephalin in spleen, adrenals and thymus glands of Sprague-Dawley rats was determined. Rats were made tolerant to and dependent on morphine by subcutaneous implantation of 6 morphine pellets (75 mg morphine in each) during a 7-day period. The tolerant-dependent (with pellets intact) and abstinent (pellets removed 18 hours earlier) rats were sacrificed. In another group, rats with pellets intact were injected with naloxone and sacrificed 10 min later (precipitated abstinence). The weights of the tissues under any of the above treatments did not change nor did the levels of methionine-enkephalin and beta-endorphin in adrenals. The level of beta-endorphin was elevated in the spleen and thymus of morphine tolerant-dependent rats, while the levels of methionine-enkephalin in rats undergoing abrupt or naloxone-precipitated abstinence were significantly higher than in their respective placebo controls. The levels of methionine-enkephalin in the thymus gland of rats with placebo and morphine pellets left intact did not differ. It is concluded that in morphine tolerant-dependent rats the levels of beta-endorphin in spleen and thymus are elevated. During abrupt and naloxone-precipitated abstinence, the levels of methionine-enkephalin in the thymus gland are significantly elevated possibly due to an inhibition of their release. Since these opioid peptides have been implicated in immunomodulation, and alterations were seen in organs controlling immune function, the present results may be helpful in explaining altered immune function in morphine dependent and abstinent states.

Adrenal Glands↗
PubMed1989

Changes in multiple opioid receptors in regions of the brain in rats treated chronically with thyroxine.

The effect of the administration of thyroxine (T4) (1 mg/kg, s.c.), to male Sprague-Dawley rats on alternate days for 18 days, on the binding of opioid ligands, [3H]Tyr-D-Ala-Gly-MePhe-Gly-ol (DAGO, mu receptors), [3H]Tyr-D-Ser-Gly-Phe-Leu-Thr (DSTLE, delta receptors) and [3H]ethylketocyclazocine (EKC, kappa receptors) to membranes of regions of the brain was determined. The chronic administration of thyroxine to rats decreased their rate of gain of body weight, increased colonic temperature and increased systolic blood pressure and heart rate, in comparison to vehicle-injected rats. The administration of thyroxine also increased the serum concentration of triiodothyronine (total T3) and thyroxine, when compared to vehicle-injected rats. The binding of [3H]DAGO to membranes of the striatum of rats treated with thyroxine was greater than in vehicle-treated rats; however, the binding to membranes of pons and medulla, amygdala, hypothalamus, midbrain and cortex in the two treatment groups did not differ. The increased binding of [3H]DAGO in rats treated with thyroxine was due to an increase in the Bmax value. The binding of [3H]DSTLE in the midbrain, hypothalamus, pons and medulla and striatum of rat treated with thyroxine and vehicle-injected rats did not differ but it was significantly less in the amygdala of rats injected with thyroxine than in vehicle-injected rats. The decreased binding in the amygdala was due to changes in the Kd value of [3H]DSTLE.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Role of neurotransmitters in fenitrothion-induced aggressive behaviour in normal and lesioned rats.

Normal and brain-lesioned (amygdala, septal and nigral regions) rats exposed to fenitrothion (10 mg/kg) for 15 subsequent days showed elevated foot-shock fighting behaviour (septal and nigral lesioned rats). Treated animals failed to perform the rotorod test and showed decreased locomotor activity followed by convulsions. The brain-lesioned rats treated with 10 mg/kg fenitrothion showed a marked decrease in the level of norepinephrine (NE) and serotonin (5-HT).

Aggression↗
PubMed1989

Brain and pituitary receptors for thyrotropin-releasing hormone in hypothyroid rats.

The effect of hypothyroidism on the thyrotropin-releasing hormone (TRH) receptors in several brain regions and pituitary of rats was determined. TRH receptors were labeled with 3H-(3-MeHis2)TRH (3H-MeTRH). Hypothyroidism was induced in male Sprague-Dawley rats by administering methimazole (0.05% w/v) in drinking water for 32 days. Rats serving as controls were given water without the methimazole. The development of a hypothyroid state was evidenced by significant decreases in colonic temperature, systolic blood pressure, heart rate and serum concentration of triiodothyronine (total T3), thyroxine and T3 uptake (T3U) as compared to control rats. The rate of gain in body weight of methimazole-treated rats was significantly lower than that of control rats. Binding of 3H-MeTRH at 2 nM concentration to membranes prepared from brain regions (striatum, hypothalamus, cortex, midbrain and pons plus medulla) of methimazole-treated and control rats did not differ. However, binding of 3H-MeTRH to pituitary membranes of methimazole-treated rats was significantly lower as compared to the pituitary of control rats. The results indicate that, in the rat, development of hypothyroidism is associated with down-regulation of pituitary TRH receptors but brain receptors remain unaffected.

Animals↗
PubMed1989

Effect of repeated administration of U-50,488H, a kappa opioid receptor agonist, on central 5-HT1 and 5-HT2 receptors in the rat.

The effect of repeated administration of U-50,488H, a kappa-opioid receptor agonist, on the development of tolerance to its analgesic effect and on the 5-HT1 and 5-HT2 receptors in the cerebral cortex and spinal cord of the rat were determined. Male Sprague-Dawley rats were injected twice daily with U-50,488H, (25 mg/kg, i.p.) or its vehicle for 4 days. The assessment of tolerance to the analgesic effect and biochemical determinations were made on day 5. Repeated administration of U-50,488H resulted in the development of tolerance to its analgesic effect. The 5-HT1 and 5-HT2 receptors were characterized by using 3H-5-hydroxytryptamine (3H-5-HT) and 3H-spiperone as the ligands and unlabeled 5-hydroxytryptamine (5-HT) and ketanserin, respectively, to determine the nonspecific binding. In the spinal cord 3H-5-HT bound to 5-HT1 receptors at a single high-affinity site with a Bmax value of 41.3 +/- 9.6 fmol/mg protein and a Kd value of 22.6 +/- 7.0 nmol/l. 3H-Spiperone bound to 5-HT2 receptors in the spinal cord with a Bmax value of 16.1 +/- 3.8 fmol/mg protein and a Kd value of 0.36 +/- 0.15 nmol/l. Repeated administration of U-50,488H to rats did not affect spinal cord 5-HT1 and 5-HT2 receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1989

Effect of chronic administration of U-50,488H on tolerance to its pharmacological actions and on multiple opioid receptors in rat brain regions and spinal cord.

The effects of chronic administration of U-50,488H (trans-3,4-dichloro-N-[2-(1-pyrrolidinyl)cyclohexyl]benzeacetamide ), a selective kappa opioid agonist, on the development of tolerance to its analgesic and hypothermic effects and on mu, delta and kappa opioid receptors in brain regions and spinal cord of male Sprague-Dawley rats were determined. Rats were injected i.p. twice daily with 25 mg/kg of U-50,488H for 4 days. The development of tolerance to the analgesic and hypothermic effects of U-50,488H was almost complete after 4 days of treatment. [3H]Tyr-D-Ala-Gly-MePhe-Gly-ol (DAMGO), [3H]Tyr-D-Ser-Gly-Phe-Leu-Thr (DSTLE) and [3H]ethylketocyclazocine (EK) were used as ligands for mu, delta and kappa opioid receptors, respectively. The binding of [3H]DAMGO to membranes prepared from various brain regions (pons + medulla, midbrain, hypothalamus, corpus striatum and cortex) and spinal cord was unaffected by chronic administration of U-50,488H. The binding of [3H]DSTLE in U-50,488H-treated rats was decreased in spinal cord and increased in corpus striatum. The binding of [3H]EK to membranes prepared from pons + medulla, midbrain, cortex and spinal cord was decreased whereas it was increased in the corpus striatum. The changes in the binding of [3H]DSTLE and [3H]EK after chronic treatment with U-50,488H were due to changes in the maximum binding values and not in the Kd values. The results indicate that, in the rat, chronic administration of U-50,488H results in the development of tolerance to its analgesic and hypothermic effects and down-regulation of kappa and delta opioid receptors in the spinal cord and an up-regulation in the corpus striatum.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1988

Cardiovascular responses to kappa opioid agonists in intact and adrenal demedullated rats.

The effects of three kappa opioid agonists namely, bremazocine, tifluadom and U-50,488H were studied on blood pressure and heart rate in urethane-anesthetized normal and bilateral adrenal demedullated rats. Bremazocine (0.2, 0.4 and 0.6 mg/kg i.v.) produced a dose-dependent decrease in heart rate, while only 0.4 mg/kg bremazocine produced marked hypotension. The effect appeared to be long lasting because even at 60 min following drug administration the decreases in both heart rate and blood pressure continued. Bilateral adrenal demedullation did not change bremazocine-induced fall in blood pressure but the bradycardia was partially blocked. Tifluadom (0.1-0.4 mg/kg i.v.) produced an initial arrest of heart beat followed by bradycardia which recovered in about 60 min. Except for a very transient fall soon after drug administration no significant effect was observed on blood pressure. In adrenal demedullated rats, tifluadom induced initial arrest of heart was not affected but the subsequent bradycardia was blocked. U-50,488H (0.2, 0.4 and 0.6 mg/kg i.v.) produced dose-dependent bradycardia and hypotension both of which were blocked following bilateral adrenal demedullation. Naltrexone methylbromide (MRZ 2663 BR), a quaternary opioid antagonist, injected 5 min prior to U-50,488H, blocked its cardiovascular effects. The results suggest that kappa opioid agonists given i.v. depress cardiovascular system and these effects are mediated through the adrenal medulla and peripheral opioid receptors. The differential effects of kappa opioid agonists on blood pressure and heart rate suggest that either the three kappa agents interact differentially at the kappa opioid receptors or the subtypes of receptors for the kappa opioid exist.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1988

An analysis of stereotyped behaviour in Mastomys natalensis.

The stereotyped behaviour was analysed in Mastomys natalensis, a species of desert rat recently introduced in laboratory practice. The components of stereotyped behaviour were similar to rat characterised by repetitive sniffing, rearing, licking, head movements and biting. Apomorphine (0.5-2.0 mg/kg), amphetamine (2.5-10 mg/kg), methylphenidate (10-30 mg/kg) and adamantanamine (10-50 mg/kg) administered intraperitoneally, induced stereotyped behaviour in dose-dependent manner. Positive response was also obtained by other drugs acting on dopamine receptors like l-dopa, GBR 12909, piribedil, tyramine, BS 9648, BS 9641 and BS 8824. Yohimbine (2 mg/kg) failed to produce any response. Apomorphine (2 mg/kg), amphetamine (10 mg/kg), methylphenidate (30 mg/kg) and piribedil (12 mg/kg) induced stereotypy which could be blocked by dopamine receptor blockers haloperidol (1 mg/kg) or pimozide (1 mg/kg) but yohimbine (2 mg/kg) an alpha adrenoceptor blocker was ineffective. Adamantanamine, piribedil and GBR 12909 enhanced the stereotypy induced by low doses of apomorphine, amphetamine and methylphenidate. The data shows that the stereotyped behaviour in Mastomys natalensis is mediated through dopaminergic mechanisms. It appears that both excitatory and inhibitory types of dopamine receptors are involved.

Animals↗
PubMed1988

Role of central histaminergic mechanism in behavioural depression (swimming despair) in mice.

The role of the central histaminergic system in depression was studied by using swimming despair test in mice - a behavioural model of depression. In this test, immobility of mice reflects a state of depression. Intracerebral (ic) injection of histamine (50-200 micrograms) increased significantly the immobility. The H1-receptor blocker mepyramine (2.5-20 mg/kg ip) had no effect while H2-receptor blocker cimetidine (100-200 micrograms ic) caused a significant decrease in immobility. The histamine induced facilitation was blocked completely by cimetidine and antidepressant drugs-imipramine and desipramine, but remained unaffected in mice pretreated with mepyramine or atropine. The H2 agonist impromidine (20-40 micrograms ic) also enhanced significantly, the immobility which was blocked by cimetidine and antidepressant drugs. It has been concluded that central H2-receptors facilitate depression and antidepressant drugs block central H2-receptors.

Animals↗
PubMed1988

Cerebral cortical 5-HT1 and 5-HT2 receptors of morphine tolerant-dependent rats.

The effect of chronic administration of morphine to rats on 5-HT1 and 5-HT2 receptors in the cerebral cortex was determined. Male Sprague-Dawley rats were implanted subcutaneously with 6 pellets of morphine (each containing 75 mg of morphine free base) during a 7 day period. Animals which served as controls were implanted with placebo pellets. The procedure for implantation of pellets produced a high degree of tolerance to and physical dependence on morphine in the rat. The tolerance to the analgesic and hyperthermic effects of morphine was demonstrated by decreased responses in the rats implanted with morphine pellet in comparison to the placebo-treated controls. The physical dependence was shown by the greater weight loss after removal of the pellet in the rats implanted with morphine pellets when compared to rats implanted with placebo pellets. The pellets were removed (withdrawn) and, after 6-8 h, the rats were sacrificed and the cerebral cortex was isolated. In another experiment the pellets were left in place (tolerant-dependent rats). The 5-HT1 and 5-HT2 receptors were characterized by using [3H]5-HT and [3H]spiroperidol as the ligands and unlabelled 5-HT and ketanserin, respectively, to determine non-specific binding. The [3H]5-HT bound to 5-HT1 receptors on membranes from the cerebral cortex of rats implanted with placebo pellets, at a single high affinity site, with a Bmax of 102 +/- 10 fmol/mg protein and a Kd of 6.02 +/- 0.98 nM. Implantation of morphine pellets, followed by removal of the pellets resulted in a 50% increase in the Bmax value of [3H]5-HT but the Kd values did not change.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Stereoselectivity of kappa-opiate receptor ligands in inhibiting the binding of [3H][3-MeHis2]thyrotrophin releasing hormone to brain membranes.

The effect of (+/-)-, (-)- and (+)-isomers of several ligands for kappa-opiate receptors on the binding of [3H][3-MeHis2]-thyrotrophin releasing hormone ([3H]MeTRH) to rat brain membranes has been determined. [3H]MeTRH bound to rat brain membranes at a single high affinity site with maximal binding capacity (Bmax) of 48 +/- 2 fmol(mg protein)-1, and an apparent dissociation constant, Kd of 4.6 +/- 0.2 nM. At a concentration of 2 nM, the specific binding of [3H]MeTRH was 12.3 +/- 0.6 fmol(mg protein)-1. The isomers of ketocyclazocine, tifluadom (1-methyl-2-(3-thienylcarbonyl) aminomethyl-5-(2-fluorophenyl) H-2,3-dihydro-1,4-benzodiazepine), and alpha-5,9-diethyl-2'-hydroxy-2-(3-furylmethyl)-6,7-benzomorphan [MR 2266 (-), MR 2267 (+)] were used for interaction studies. The (-)-isomer of each of the above drugs was more potent than the (+)-form in inhibiting the binding of [3H]MeTRH to brain membranes, whereas the (+/-)-forms had activity intermediate between (-)- and (+)-forms. The order of activity of kappa-ligands was tifluadom greater than MR 2266 greater than ketocyclazocine. It is concluded that kappa-opiate drugs inhibit the binding of [3H]MeTRH to brain membranes in a stereoselective manner with tifluadom being the most potent drug.

Animals↗
PubMed1988

Differential alteration in striatal dopaminergic and cortical serotonergic receptors induced by repeated administration of haloperidol or centbutindole in rats.

Centbutindole is a new neuroleptic drug having a pharmacological profile similar to haloperidol, but it does not cause hypothermia and has a higher separation between doses causing catalepsy and neurolepsy. The interactions of centbutindole with striatal dopamine and cortical 5-HT2 receptors have been studied along with haloperidol following 3 weeks of administration. Rats received haloperidol (1.0 mg/kg, p.o.), centbutindole (0.5 mg/kg, p.o.) or saline daily for 21 days. Following drug withdrawal for 3 days, apomorphine (0.1-1.0 mg/kg, i.p.) or 5-hydroxytryptamine (5-HTP, 50-200 mg/kg, i.p.) was injected. Apomorphine-induced stereotyped behaviour was potentiated in the haloperidol-treated rats, while the 5-HTP-induced behavioural syndrome was increased in centbutindole-treated rats. Receptor binding studies indicated an increase in the maximal binding capacity Bmax of striatal dopamine receptor (29.4%) in haloperidol-treated and of cortical 5-HT2 receptor (17.8%) in centbutindole-treated animals. No change in the apparent dissociation constant Kd was observed. It is concluded that repeated treatment with haloperidol produced striatal dopamine receptor supersensitivity while centbutindole treatment produced cortical serotonergic receptor supersensitivity.

5-Hydroxytryptophan↗