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Biomedical subjects

R K Bhatnagar

Publications and source records attributed to R K Bhatnagar.

At least 91 records · Page 5Linked to original sources
PubMed1981

Opiate receptor ontogeny and morphine-induced effects: influence of chronic footshock stress in preweanling rats.

The ontogeny of opiate receptors was examined in various CNS regions of preweanling rats which received either daily inescapable footshock stress, exposure to a footshock apparatus without shock, or no handling from birth to 21 days of age. At 21 days of age, each of these treatment groups was also assessed for morphine-induced changes in activity, hot-plate paw-lick latency, and core body temperature. Marked regional differences in [3H]naloxone binding capacity were observed from 7 to 21 days of age in spinal cord, medulla-pons, midbrain, hypothalamus, striatum, and cortex. Caudal regions approached adult-like [3H]naloxone binding before rostral regions. The normal ontogeny of opiate receptors was not significantly influenced by the chronic footshock treatment. However, footshock treatment significantly reduced the efficacy of morphine (2 mg/kg) in producing hypoactive and antinociceptive effects, but not in producing a hyperthermic effect. These results demonstrate that stress-related changes in the behavioral efficacy of morphine do not necessarily depend upon changes in those opiate receptor populations that bind naloxone.

Aging↗
PubMed1981

Dopamine receptor stimulating activity of 5-hydroxy-6-methyl-2-aminotetralin derivatives.

The effects of 5-hydroxy-6-methyl-2-aminotetralins were evaluated for central and presynaptic peripheral dopaminergic activity. Di-ethyl (DK-121) and di-propyl (DK-118) derivatives inhibited the tachycardia produced by postganglionic cardioaccelerator nerve stimulation in the cat. This effect was blocked by haloperidol (100 micrograms/kg). DK-118 inhibited stimulation-induced contraction of the cat nictitating membrane. The pressor response produced by lumbar sympathetic chain stimulation in the isolated hindlimb of the cat was inhibited by DK-118 following intravenous administration. Reflex sympathetic activation produced by 30 sec bilateral carotid occlusion was also inhibited by DK-118 in the dog. Centrally, DK-118 caused contralateral circling behavior in rats who had unilateral lesions of the caudate nucleus. DK-118 did not effect DOPA levels in either the caudate nucleus or olfactory tubercle. In contrast, DK-121 decreased DOPA levels in the caudate nucleus but did not produce circling behavior in rats. Both compounds have weak emetic activity in dogs. These results suggest that DK-121 and DK-118 possess stimulant properties on dopaminergic receptors in the central and peripheral nervous system. However, DK-121 does not appear to stimulate postsynaptic dopamine receptors in the central nervous system.

Animals↗
PubMed1980

Regenerative critical periods for locus coeruleus in postnatal rat pups following intracisternal 6-hydroxydopamine: a model of noradrenergic development.

Rat pups were injected intracisternally with 20, 40 or 80 microgram of 6-hydroxydopamine (6-OHDA) at various ages over the first 12 postnatal days in order to determine the critical period of the noradrenergic regenerative-sprouting response in the cerebellum. Twenty-four hours after the treatment NE fibers in the cerebellum had become extensively degenerated. NE levels were reduced by greater than 90-95% and histofluorescence microscopy revealed an absence of innervation except for lesioned axon stumps in the basal white matter and peduncles. The 80 microgram dose produced considerable cellular degeneration in the locus coeruleus and no regenerative growth was seen to follow this treatment. Following the two lower doses, however, regenerative growth did occur. This was maximal in those rats treated closest to birth and declined progressively to become insignificant in rats which were treated on postnatal days 5-12, depending upon the cerebellar subregion. This decline in regenerative potential paralleled the time course for development of NE levels in control cerebella. For this reason the mechanism(s) controlling noradrenergic developmental and regenerative growth in the cerebellum appear to be similar. Such regenerative growth may thus be a useful model for the study of developmental growth of locus coeruleus axons. Contrary to the cerebellar projection, regenerative growth of the forebrain noradrenergic projection was not detected until the rats were between 7 and 12 days old at the time of treatment. This regeneration in the cerebral cortex was preceded by incomplete initial destruction of NE fibers there, in apparent similarity to regenerative growth described to occur in the adult rat forebrain.

Adrenergic Fibers↗
PubMed1980

Uterine catecholamines and prostaglandins during the estrous cycle of the rat.

The uterine contents of norepinephrine, epinephrine, dopamine, and prostaglandins F and E were determined on each day of the rat estrous cycle. Catecholamines were determined by high performance liquid chromatography with electrochemical detection (HPLC-EC) as well as by a radioenzymatic technique; prostaglandins were quantitated by RIA. The norepinephrine and dopamine values obtained by the radioenzymatic assay were approximately 1.5 times as high as the values obtained by HPLC-EC (norepinephrine, 285 vs. 188 ng/g; dopamine, 11.0 vs. 7.5 ng/g). Despite this difference in levels, both analytic techniques showed a decline in uterine norepinephrine from diestrus to estrus, followed by a significant (P less than 0.01) increase in norepinephrine on the day of metestrus. A cyclic pattern was also revealed for uterine dopamine concentration. There was a decline in dopamine concentration from diestrus to proestrus (radioenzymatic, P less than 0.01), followed by a return to high levels at metestrus (HPLC-EC). Epinephrine levels were low (undetectable by radioenzymatic assay; 24 ng/g by HPLC-EC) and showed no variation during the estrous cycle. Prostaglandin F was uniformly higher than prostaglandin E (10 vs. 2.5 ng/uterus). Significant increases in the uterine contents of both prostaglandins were shown on the day of proestrus.

Animals↗
PubMed1980

Intracisternal dose-response analysis of 6-hydroxydopamine-induced noradrenergic sprouting in the neonatal rat cerebellum.

The dose-response relationship between neonatal 6-hydroxydopamine and noradrenergic regenerative sprouting in the cerebellum was characterized by using intracisternal doses of 10 to 80 micrograms of the drug. Noradrenergic regeneration was assessed in seven subregions of the cerebellum by measurement of norepinephrine (NE) levels once the rats were one-month-old. Regenerative sprouting occurred to a significant extent at drug doses between 10 to 40 micrograms, with peak NE elevations occurring after a 20-microgram dose. Recovery of NE was not uniform throughout the cerebellum but was maximal in the anterior vermis and minimal in the posterior vermis. An 80-microgram dose produced near total loss of cerebellar NE. This is contrasted to the cerebral cortical noradrenergic innervation which responded with significant long-term degeneration to a dose as low as 10 micrograms. In both areas, the initial effect of the drug treatment was to reduce NE levels by 95% or more. A couple of conclusions can be made. The magnitude of the difference between the cerebellar and cerebral cortical dose-response relationships is consistent with a regenerative mechanism subserving the recovery of NE in the cerebellum. Secondly, the increase of NE in the cerebellum is reciprocally related to destruction of the forebrain noradrenergic projection.

Animals↗
PubMed1979

Distribution of hypertrophied locus coeruleus projection to adult cerebellum after neonatal 6-hydroxydopamine.

Following treatment as neonates with a high subcutaneous dose of 6-hydroxydopamine (6-OHDA), the projections of the locus coeruleus were mapped in the brains of adult rats. This was done using the technique of unilateral lesions in the nucleus followed by simultaneous determinations of norepinephrine (NE) levels, dopamine-beta-hydroxylase (DBH) activity and synaptosomal [3H]NE uptake in various terminal areas. In particular the cerebellum was subdivided into 3 areas in order to assess any changes from normal in the distribution of the hypertrophied noradrenergic projections here. In vehicle-control rats the lesions resulted in an 80--85% loss of NE in the parietal cortex ipsilateral to the lesion and a 15--20% loss contralaterally. In the control cerebellum the locus coeruleus projection, based upon changes in all 3 markers, is distributed 2/3 ipsilaterally and 1/3 contralaterally with the same pattern present in all 3 subregions. The neonatal 6-OHDA treatment resulted in virtually complete loss of noradrenergic terminals in the cerebral cortex. Following neonatal 6-OHDA treatment cerebellar levels of NE, DBH and [3H]NE uptake increased by between 20--60%, with the smallest increases occurring in [3H]NE uptake. In these rats the locus coeruleus accounted for at least 75--80% of the cerebellar noradrenergic parameters. Unlike control rats however, the lesions in these rats produced only ipsilateral decreases in NE and DBH. On the other hand changes in [3H]NE uptake indicated a normal 2/3 ipsilateral, 1/3 contralateral pattern. It is suggested that two separable events occur in the noradrenergic projection to the cerebellum. The first is the regeneration of an increased number of nerve terminals, or sprouting, and the second is a build-up of synaptic vesicles, or collateral accumulation. The sprouting, judging from the [3H]NE uptake data, occurs with apparently normal distribution, but the accumulation of NE and DBH is confined predominantly to the ipsilaterally projecting axon terminals. This may be the consequence of collateral accumulation resulting from the degeneration of the largely ipsilateral coeruleocortical projection.

Animals↗
PubMed1979

Regional development of norepinephrine, dopamine-beta-hydroxylase and tyrosine hydroxylase in the rat brain subsequent to neonatal treatment with subcutaneous 6-hydroxydopamine.

Neonatal rats were injected subcutaneously with 100 mg/kg 6-hydroxydopamine (6-OHDA), or vehicle, on postnatal days 1, 2 and 3. At several times thereafter, determinations of tyrosine hydroxylase (TOH) and dopamine-beta-hydroxylase (DBH) activities, and norepinephrine (NE) concentration were made in the parietal cortex, cerebellum and pons-medulla in order to assess the extent of initial noradrenergic degeneration induced, and the rate of any ensuing regeneration. By the day following completion of the treatment (postnatal day 4), degeneration of noradrenergic terminals in the parietal cortex and cerebellum was very extensive, with NE levels and DBH activities reduced by more than 80%, and TOH activities reduced by 50%. In the parietal cortex noradrenergic degeneration remained virtually complete; and 9 and 70 days postnatal NE concentration and DBH and TOH activities were all decreased by more than 90--95%. In the cerebellum a progressive regeneration and apparent sprouting of NE fibers was observed. By postnatal day 9, NE, DBH and TOH in this tissue had all recovered to near control levels, and by day 70 these measures exceeded control levels by 95%, 115% and 50% respectively. In the pons-medulla, the initial effect of 6-OHDA on any of the measured parameters was negligible. By postnatal day 9 an increase in NE concentration was apparent, which increased further by day 70 to surpass the control level by 70%. At this same time DBH activity was increased by only 15% and TOH activity was unchanged. Separate analysis of the rostral half of the pons, which contains the locus coeruleus, revealed that on day 70 NE and DBH levels were increased much more substantially than in the whole pons-medulla, and TOH activity was also significantly elevated. This data indicates that the initial amount of degeneration induced by the 6-OHDA treatment is similar in both the parietal cortex and cerebellum, but regeneration proceeds only in the cerebellum. This suggests that noradrenergic fiber growth and regeneration in each target tissue is under independent regulation, possibly by the individual target neurons themselves.

Animals↗
PubMed1979

Assessment of the effects of neonatal subcutaneous 6-hydroxydopamine on noradrenergic and dopaminergic innervation of the cerebral cortex.

Female rats, treated at birth with 6-hydroxydopamine (3 x 100 mg/kg s.c. at 24 h intervals) or vehicle, were subjected at 112 days of age to unilateral electrolytic lesions of the locus coeruleus. Two weeks later regions of the telencephalon, both ipsi- and contralateral to the lesion, were simultaneously assayed for norepinephrine (NE) and dopamine (DA) content, and for tyrosine hydroxylase (TOH) and dopamine-beta-hydroxylase (DBH) activities. In the vehicle-treated rats the lesion resulted in at least an 80% reduction of NE and DBH on the ipsilateral side, relative to the contralateral side. TOH was reduced to a similar extent only in the parietal cortex and hippocampus. In the prefrontal cortex and cingulate gyrus TOH was decreased by only 31% and 64% respectively; the remainder was interpreted to be associated with projections of the mesocortical dopamine system. From this data it was possible to calculate that the ratio of TOH to DA in dopaminergic terminals is about 10-fold greater than the ratio of TOH to NE in noradrenergic terminals. Neonatal 6-hydroxydopamine treatment resulted in practically total elimination of noradrenergic terminals throughout the telencephalon, and the locus coeruleus lesion had no additional effect. The drug treatment produced no significant change in DA content or in the TOH to DA ratio in the prefrontal cortex and cingulate gyrus, indicating complete sparing of the mesocortical DA projections.

Animals↗
PubMed1979

Humoral regulation of vascular resistance after 30 days of pulmonary artery constriction.

In an earlier study of guinea pigs with constriction of the pulmonary artery (PA) for 30 days, hindquarters' vascular resistance was maintained primarily by humoral mechanisms. In the present study, we investigated the contribution of circulating catecholamines, angiotensin II, and other constrictor stimuli to hindquarters' vascular resistance by observing vasodilator responses to specific competitive antagonists. Pressure-flow curves indicated vascular resistances in isolated, perfused, sympathectomized hindquarters of anesthetized guinea pigs. Phentolamine produced significantly greater (P less than 0.05) vasodilatation in animals with constriction of pulmonary artery than in sham animals [Sar1-Ala8]angiotensin II produced no vasodilation in either group. After alpha-adrenergic blockade, papaverine produced similar vasodilatation and similar final perfusion pressures in both groups. It appears that circulating catecholamines and augmented vasoconstrictor responsiveness to norepinephrine are totally responsible for the increased humoral regulation of vascular resistance in this experimental model of right ventricular hypertrophy.

Angiotensin II↗
PubMed1978

The effects of subhypnotic doses of ethanol on regional catecholamine turnover.

A 2 g/kg dose of ethanol given intraperitoneally to rats significantly reduced the turnover of dopamine in the substantia nigra and caudate nucleus, increased dopamine turnover in the olfactory tubercle and had no effect on dopamine turnover in the nucleus accumbens, amygdala and hypothalamus. The same dose of ethanol decreased the probenecid-induced homovanillic acid accumulation in the caudate nucleus. The turnover of norepinephrine was also decreased in hypothalamus and increased in the pons medulla region. No change in norepinephrine turnover was observed in frontal cortex, parietal cortex, cerebellum, amygdala, hippocampus and locus ceruleus region. The distribution of ethanol was similar in cortex, caudate nucleus, hypothalamus and pons-medulla. Catecholamine turnover in different brain regions seems to be differentially sensitive to the effects of ethanol, with most regions being unaffected by ethanol.

Animals↗
PubMed1977

Histochemical and biochemical characterization of the rat paracervical ganglion.

The nature and identity of the catecholamines in the paracervical ganglion and superior cervical ganglion small, intensely fluorescent (SIF) cells were investigated using fluorescence histochemical and immunohistochemical techniques. The paracervical ganglion SIF cells were found to contain norepinephrine and the superior cervical ganglion SIF cells, dopamine. The norepinephrine content of the paracervical ganglion SIF cells averaged about 72 ng/ganglion and did not change during the rat estrus cycle. The activity of the enzyme tyrosine hydroxylase in the PCG was very low (about 0.48 nmoles DOPA formed/h/mg protein) and was about 1/50th of the activity of the enzyme in the SCG, where it averaged about 23.90 nmoles DOPA formed/h/mg protein. These experiments suggested that the paracervical ganglion has large numbers of norepinephrine containing SIF cells with a relatively slow turnover of their catecholamine content.

Adrenal Medulla↗
PubMed1975

Differentiation between stains of human blood and blood of monkey.

The precipitin tube test fails to differentiate between blood stains of closely related animals such as man and monkey because of the close similarity between antigenic determinants of serum proteins of such closely related species. The quantitative precipitin technique cannot be applied to forensic work. This paper cites a case where definite opinion on the species of origin of some blood stains suspected to have come from a monkey was possible. In the method used, extracts of the questioned stain were tested with similar extracts of known human and known monkey blood stains against human globulin antiserum, by comparative double diffusion method in agar gel on microslides.

Animals↗