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Biomedical subjects

R B Rastogi

Publications and source records attributed to R B Rastogi.

At least 19 recordsLinked to original sources
PubMed1983

Behavioural and biochemical alterations following haloperidol treatment and withdrawal: the animal model of tardive dyskinesia reexamined.

Behavioural and biochemical studies were carried out in rats given a single daily dose (1 mg/kg, i.p.) of haloperidol for 30 days and subsequently withdrawn for 7 days. Long-term administration of haloperidol resulted in supersensitivity of dopamine receptors. This was manifested by enhanced stereotypic biting, rearing, locomotor and floor activity of haloperidol withdrawn rats when challenged to a low dose of apomorphine (0.5 mg/kg, s.c.) on the 8th day. Chronic haloperidol treatment significantly decreased dopamine synthesis and release as evidenced by low activity of tyrosine hydroxylase and low level of homovanillic acid in striatum. Dopamine levels did not change in the frontal cortex, striatum and midbrain. Haloperidol treatment significantly increased striatal gamma-aminobutyric acid content and glutamic acid decarboxylase activity by 17% and 16% respectively. The decreased tyrosine hydroxylase activity and homovanillic acid level in corpus striatum might, in part, be due to an inhibitory effect of GABAergic neurons on dopaminergic system. Rats withdrawn from chronic haloperidol treatment showed significant increases in GABA level and glutamic acid decarboxylase activity. This probably resulted in further inhibition of dopamine release as evidenced by marked accumulation of dopamine in the corpus striatum and midbrain. No significant alterations in the endogenous levels of norepinephrine, 5-hydroxytryptamine and 5-hydroxyindoleacetic acid were observed in haloperidol-treated and subsequently withdrawn rats. These data suggest that chronic haloperidol treatment and subsequent withdrawal results in the development of behavioural dopamine supersensitivity as well as biochemical alterations in dopaminergic and GABAergic system. The changes in these two neuronal systems seem to be interrelated.

Animals↗
PubMed1982

MIF-1: effects on norepinephrine, dopamine and serotonin metabolism in certain discrete brain regions.

A single injection of melanocyte-stimulating hormone inhibitory factor (MIF-1) in a dose of 3 mg/kg IP produced no significant effect on dopamine turnover. However, a dose of 5 mg/kg increased striatal tyrosine hydroxylase activity by 25% and homovanillic acid level by 27% when compared to control values. No change in either parameter was detected in olfactory tubercles. Dopamine levels also were elevated in striatum, pons-medulla and cerebral cortex in rats receiving 5 mg/kg dose of MIF-1. In olfactory tubercles, dopamine levels were however, reduced to 71% of control values taken as 100%. The concentration of norepinephrine tended to increase in several brain areas examined but, the change was statistically significant only in olfactory tubercles and cerebral cortex. The level of norepinephrine metabolite, 3-methoxy-4-hydroxyphenylethylene glycol, was lowered to 63% in whole brain of animals given MIF-1 at the dose of 5 mg/kg. These data suggest that MIF-1 enhances the turnover of dopamine and norepinephrine in the brain. However, MIF-1 treatment seemed to produce no consistent change in brain serotonin turnover. In striatum and cortex, this neuropeptide increased serotonin but elevated the level of its metabolite, 5-hydroxyindoleacetic acid indicating that the release of this brain amine was decreased in these two brain regions. The levels of 5-hydroxyindoleacetic acid were enhanced in hypothalamus and pons-medulla regardless of the dose of MIF-1 administered.

Animals↗
PubMed1982

Comparative effects of short- and long-term treatment with neuroleptics on behavioural activity as well as dopamine turnover in striatum.

1. Single injection of haloperidol (2 mg/kg, i.p.) or chlorpromazine (10 mg/kg, i.p.) produced an activation of dopamine synthesis and turnover as evidenced by increased activity of tyrosine hydroxylase and higher levels of homovanillic acid in the striatum of rats. 2. The endogenous concentration of dopamine remained unchanged in striatum and other brain regions examined, except in hippocampus where it was slightly (20%), but significantly decreased by acute haloperidol treatment. 3. In contrast, long-term treatment with neuroleptics over a period of 21 days decreased the synthesis and turnover of dopamine in the striatum. Whereas short-term treatment with chlorpromazine and haloperidol produced marked sedation, chronic treatment enhanced spontaneous locomotor activity by 20 and 26% and sniffing frequency by 19 and 24%, respectively. 4. Our data demonstrate that tolerance develops to the stimulating effect of haloperidol and chlorpromazine on striatal dopamine turnover. This adaptive change might be responsible for the emergence of clinical effects. 5. It is suggested that after repeated treatment, "chemical denervation" occurs as a result of chronic blockade of dopaminergic transmission in the striatum and that the proliferation of dopamine receptors (i.e. supersensitivity) is probably responsible for hyperactivity and overt sniffing behaviour.

Animals↗
PubMed1981

MK-771 enhances the turnover of norepinephrine in brain.

Single injection of MK-771, an analog of thyrotropin-releasing hormone (10 mg/kg) increased the soluble tyrosine hydroxylase activity in striatum and olfactory tubercles by 22% and 31%. The endogenous levels of norepinephrine in olfactory tubercles, striatum, hypothalamus, mid-brain, pons medulla and cerebral cortex remained unchanged; in hippocampus, it was lowered to 71% of controls. Furthermore, the concentration of 3-methoxy-4-hydroxy-phenylethylene glycol was enhanced by 33%. Data suggest that MK-771 increases the synthesis and release of norepinephrine and that MK-771 elicits its CNS stimulant action partly by augmenting the turnover of this biogenic amine.

Animals↗
PubMed1979

Evidence that chronic apomorphine treatment enhances 5-hydroxytryptamine metabolism in brains of normal and neonatally hyperthyroid rats.

Daily injection of L-triiodothyronine (10 microgram/100 g, s.c.) for 30 days to neonatal rats significantly enhanced the metabolism of 5-hydroxytryptamine as reflected by increased tryptophan hydroxylase activity and 5-hydroxyindoleacetic acid levels of certain discrete brain regions. However, neonatal L-triiodothyronine treatment produced no change in 3H-5-hydroxytryptamine uptake by crude synaptosomes. Chronic treatment with apomorphine (1 mg/kg/day, s.c.) for 15 days, beginning from 15 days of age, increased tryptophan hydroxylase activity as well as 5-hydroxytryptamine and 5-hydroxyindoleacetic acid levels and blocked the uptake of 3H-labelled serotonin in crude synaptosomes of normal and L-triiodothyronine-treated animals. Furthermore, apomorphine (which is known to indirectly stimulate 5-hydroxytryptaminergic neurons) produced a greater increase in tryptophan hydroxylase and 5-hydroxyindoleacetic acid in the mid-brain region of neonatally hyperthyroid animals as compared to normal rats. These data indicate that excess thyroid hormone in early life not only increases the turnover of brain 5-hydroxytruptamine, but also enhances the sensitivity of dopamine receptor sites. thus amplifying the stimulating action of apomorphine. Our findings also suggest that thyroid hormone in early life advances the overall development of monoaminergic systems in the brain.

Animals↗
PubMed1979

Effect of testosterone and 6-hydroxydopamine treatment on the metabolism of catecholamine and 5-hydroxytryptamine in methylcholanthrene-induced prostate carcinoma of rats.

The precursors tyrosine and tryptophan as well as the synthesizing and deaminating enzymes of catecholamines have been identified in methylcholanthrene-induced prostatic carcinoma of rats. Tyrosine hydroxylase, monoamine oxidase, catechol O-methyltransferase, dopamine, 5-hydroxytryptamine, and 5-hydroxyindoleacetic acid seemed to be neoplastic in origin, since electron microscopic studies failed to reveal the presence of any neuronal elements in this squamous epithelial cell carcinoma. Castration of rats significantly reduced the activity of tyrosine hydroxylase and the levels of tyrosine, dopamine, tryptophan, 5-hydroxytryptamine, and 5-hydroxyindoleacetic acid in prostate tumors. The changes appeared to be androgen specific since reintroduction of testosterone restored several of these biochemical parameters virtually to control limits. Chemical sympathectomy induced by 6-hydroxydopamine failed to alter monoamine metabolism; however, the prostatic tumor grown in 6-hydroxydopamine-treated rats showed significantly (32%) less necrosis than those grown in normal animals.

Animals↗
PubMed1978

The effect of thyroid hormone on serotonergic neurones: depletion of serotonin in discrete brain areas of developing hypothyroid rats.

A single intraperitoneal injection of 131I in a dose of 200muCi in 1-day-old rats induced hypothyroidism and decreased the activity of tryptophan hydroxylase in mid-brain region. The levels of 5-hydroxytryptamine also were reduced in cerebellum, mid-brain and striatum by 22%, 29% and 31%, respectively. By contrast, the levels of its metabolite, 5-hydroxyindoleacetic acid, were significantly increased in cerebellum, mid-brain and striatal region. To ascertain whether changes induced by neonatal radiothyroidectomy were specific, the effect of replacement thyroid hormone therapy was studied on 5-hydroxytryptamine metabolism. Daily administration of L-triiodothyronine (10 microgram/100g s.c.) for 25 days beginning from five days after radio-iodine treatment enhanced tryptophan hydroxylase activity, tryptophan and 5-hydroxytryptamine levels to values seen in normal rats of the corresponding age group. The concentration of 5-hydroxyindoleacetic acid decreased following L-triiodothyronine treatment. Furthermore, when replacement therapy with L-triiodothyronine was postponed until adulthood, no significant effects could be seen on various parameters related to 5-hydroxytryptamine metabolism. Our data demonstrate that deficiency of thyroid hormone in early life disrupts the normal upsurge of 5-hydroxytryptamine metabolism in brain. A critical period exists in early life of rats during which thyroid hormone must be present for the optimal development of 5-hydroxytryptamine metabolizing systems in maturing brain.

Animals↗
PubMed1978

Adrenocorticoids control 5-hydroxytryptamine metabolism in rat brain.

The influence of surgical adrenalectomy was examined on the biosynthetic capacity for 5-hydroxytryptamine of rat brain. The results demonstrate that adrenalectomy decreased tryptophan hydroxylase activity and its substrate tryptophan in the brain stem. A parallel change in the concentration of 5-hydroxytryptamine was seen in brain stem and striatal region of adrenalectomized rats. In contrast, the level of 5-hydroxyindoleacetic acid was significantly elevated in both of these brain regions. Replacement therapy with corticosterone (10 mg/kg i.p.) produced time-dependent increases in tryptophan, tryptophan hydroxylase and 5-hydroxytryptamine and decreases in 5-hydroxyindoleacetic acid levels. Alterations in these neurochemical parameters were more conspicuous in adrenalectomized rats receiving corticosterone for 7 days as compared to those given only for 3 days. Our data demonstrate that adrenocortical hormones regulate brain 5-hydroxytryptamine synthesis probably by enhancing both the levels of tryptophan and the activity of rate-limiting enzyme tryptophan hydroxylase. It is postulated that emotional instability seen during altered adrenocortical function might partly be associated with abnormal metabolism of central 5-hydroxytryptamine.

Adrenal Cortex Hormones↗
PubMed1978

Effect of a new benzodiazepine bromazepam on locomotor performance and brain monoamine metabolism.

Administration of a single dose (10 mg/kg) of a relatively new benzodiazepine, bromazepam to rats markedly suppressed their spontaneous locomotor activity. Hypomobility became apparent 15 min after the injection and remained significantly lower during the period of observation for 6 hours when locomotor activity was 27% of controls. Following 2 hours after bromazepam treatment, no change was noted in tyrosine levels and tyrosine hydroxylase activity in striatum or rate of catecholamine synthesis in synaptosomal preparation (P2 pellet). However, the endogenous levels of norepinephrine, dopamine and 5-hydroxytryptamine were significantly increased not only in several brain areas examined, but also in P2 pellet. Bromazepam failed to change 3H-norepinephrine and 3H-5-hydroxytryptamine uptake in synaptosomes suggesting that the increased levels of monoamines are not related to laterations in uptake mechanisms, but probably to a diminished release. This is supported by the data on striatal homovanillic acid and whole brain 4-hydroxy-3-methoxyphenyl glycol whose concentrations were significantly lowered following a single injection of this benzodiazepine. However, bromazepam increased 5-hydroxyindole-acetic acid levels in hypothalamus, mid-brain and pons-medulla. The present study demonstrates that bromazepam elicits its tranquilizing action by lowering the release of catecholamines in brain; however, its anti-anxiety action might be associated with a reduction in 5-hydroxytryptamine turn over. Our data also suggest that bromazepam is almost as potent as diazepam in altering the metabolism of certain putative neurotransmitters in brain.

Amines↗
PubMed1978

Evidence for the role of adrenocortical hormones in the regulation of noradrenaline and dopamine metabolism in certain brain areas.

1 Bilateral adrenalectomy suppressed body growth and increased the activity of tyrosine hydroxylase in rat striatum in a time-dependent manner. Fifteen days after adrenalectomy, the concentrations of noradrenaline were decreased significantly in hypothalamus and striatum, as were those of dopamine in brain stem and striatum. 2 Catechol-O-methyltransferase failed to change in response to adrenalectomy, but the activity of monoamine oxidase in cortex was significantly increased 7 days after surgery. These changes in various neurochemical parameters were even more pronounced 15 days after adrenal ablation. 3 Administration of corticosterone (10 mg/kg i.p.) to adrenalectomized rats effectively reversed the observed effects on brain amine metabolism. Corticosterone treatment for 7 days beginning from the 8th day of adrenalectomy virtually restored the concentrations of noradrenaline and dopamine as well as the activities of striatal tyrosine hydroxylase and cerebrocortical monoamine oxidase to the values seen for sham-operated controls. 4 Our data suggest that changes seen in brain noradrenaline and dopamine of adrenalectomized rats are specific to adrenocortical steroids and that these hormones play a role in the regulation of catecholamine formation.

Adrenal Cortex Hormones↗