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Biomedical subjects

P Slater

Publications and source records attributed to P Slater.

At least 91 records · Page 5Linked to original sources

Effects of mammalian and avian neurotensins and neurotensin fragments on wet-dog shaking and body temperature in the rat.

The ability of mammalian and avian neurotensins and some neurotensin fragments to reduce wet-dog shaking (WDS) induced by thyrotrophin-releasing hormone (TRH) and to influence rectal temperature was tested after their injection into the periaqueductal grey region of male rats. Both neurotensins inhibited TRH-induced WDS and reduced rectal temperature by 2 degrees C; this latter effect was prevented by prior TRH administration. Of the four neurotensin fragments tested, both (1-8)- and (8-13)-neurotensin reduced WDS but only (8-13)-neurotensin reduced rectal temperature significantly. (1-6)- and (1-11)-neurotensin were without effect in either test system. From the activity of the various peptides, further examples of the mutual antagonism between TRH and neurotensin have been demonstrated. It is suggested that there is a possible role for neurotensin in controlling body temperature via the periaqueductal grey and that this may be one function of neurotensin in avian species; there may also be more than one receptor system binding neurotensin in the brain.

Animals↗

Bone mineral status of lactating mothers of different ages.

To determine the effect of age on the bone mineralization of lactating mothers, 48 healthy mothers were evaluated at 2 and 16 weeks post partum. All mothers were divided into three age groups: less than or equal to 18 years, 19 to 30 years, and greater than 31 years old. At 2 and 16 weeks post partum, blood was drawn for measurement of serum calcium, phosphorus, alkaline phosphatase, and 25-hydroxy vitamin D. Bone mineral content was measured by photon absorptiometry. Dietary history was also recorded. At both 2 and 16 weeks, there were no differences in the serum values or bone mineral content among the three age groups. However, there was a decrease in the bone mineral content between the 2 and 16 weeks' values in the less than or equal to 18 years age group, 1.049 +/- 0.088 versus 0.895 +/- 0.051 gm/cm (p less than 0.05). Dietary intakes were similar among the three groups, but only one of seven mothers less than or equal to 18 years of age met the recommended dietary allowance for calcium or phosphorus, as compared to six of seven older mothers who met the recommended dietary allowance for calcium or phosphorus (p less than 0.01). We conclude that young lactating mothers less than or equal to 18 years old at risk for bone demineralization because of low dietary intakes of calcium or phosphorus.

Adolescent↗

Autoradiographic demonstration of binding sites for [3H]desipramine in rat brain.

Many of the characteristics of [3H]desipramine ([3H]DMI) binding sites, previously established with brain homogenates, were confirmed in slide-mounted sections of rat forebrain. A 1:1 ratio of specific to non-specific binding was established. The proportion of specifically bound [3H]DMI was reduced in brain sections from rats pretreated with 6-hydroxydopamine but not with 5,6-dihydroxytryptamine. High resolution localization of [3H]DMI binding sites was achieved by exposing the sections to tritium-sensitive film.

Animals↗

Effects of striatal and pallidal lesions and intrapallidal GABA and opiate drugs on tremorine-induced rigidity in the rat.

Tremorine-induced hindlimb rigidity was prevented by the neurotoxin kainic acid in one neostriatum. A unilateral globus pallidus (GP) electrolesion reduced the tone of the contralateral leg (CL) and differentially modified tremorine rigidity. The ipsilateral leg rigidity was reduced and the CL rigidity was increased. Resting tone and tremorine-induced rigidity were measured in CL after injection in one GP of drugs that modify pallidal GABA function. The GABA drugs tested in GP had no consistent effects on resting limb tone. By contrast, baclofen and muscimol, agonists for GABA receptors, both prevented tremorine rigidity, whereas the antagonists bicuculline and picrotoxin increased rigidity. Opiate receptor agonists in GP did not effect tone of rigidity but naltrexone prevented rigidity in CL leg. The findings suggest a close involvement of GP in mediating cholinergic limb rigidity.

Animals↗

Role of acetylcholine and dopamine in myoclonus induced by intrastriatal picrotoxin.

Rats injected intrastriatally with picrotoxin and carbachol showed sustained myoclonic jerks of the contralateral forelimb. The role of acetylcholine and dopamine in picrotoxin myoclonus was examined by measuring the effects of intrastriatal pharmacological agents on the frequency and intensity of the jerks. Atropine and hemicholinium-3, which reduce acetylcholine function, antagonized the myoclonus. Apomorphine, which has been shown to reduce striatal dopamine function via "autoreceptors", potentiated the jerking, whereas D-amphetamine antagonized the myoclonus. The findings are discussed in relation to proposed interconnections of striatal neurones.

Acetylcholine↗

Role of globus pallidus GABA and opiate receptors in apomorphine circling in nigro-striatal lesioned rats.

The effect of lesioning the ipsilateral globus pallidus (GP) on apomorphine-induced circling in nigro-striatal lesioned rats was investigated. A GP electrolesion almost abolished circling whereas a kainic acid lesion partly antagonized circling. Drugs that affect GABA and opiate receptors were injected in GP through a cannula. Circling was antagonized by the GABA antagonists picrotoxin and bicuculline, the GABA agonist muscimol and by baclofen. Opiate receptor agonists including morphine, levorphanol, [D-Ala2, D-Leu5]-enkephalin and beta-endorphin had no effect on circling in GP. Ethylketazocine caused a pronounced, naloxone-reversible slowing of apomorphine circling. Apomorphine-induced circling behaviour may be modulated by GP GABA receptors and kappa-type opiate receptors.

Animals↗

Effects of intrapallidal drugs on hyperactivity induced by nucleus accumbens dopamine receptor stimulation.

The effect of manipulating globus pallidus (GP) transmitters on the locomotor hyperactivity induced by administration of the dopamine agonist ADTN in the nucleus accumbens was investigated in rats with permanent intracerebral cannulae. Hyperactivity was antagonized by the GABA agonists muscimol and baclofen and the GABA antagonist bicuculline. Atropine, ADTN and ethylketazocine in GP had no effects on the response. Both morphine and the 5-HT agonist 5-methoxy-N,N-dimethyltryptamine prevented the hyperactivity. The findings emphasize the role of GP GABA in the NA-induced hyperactivity and provide information about the functions of some other GP transmitters.

Animals↗

Effects of lesioning basal ganglia nuclei and output pathways on tremorine-induced tremor in rats.

The tremor produced by muscarinic cholinomimetics is believed to originate in the neostriatum but the efferent pathways are unknown. The intensity and frequency of tremor induced by tremorine was measured in the hindlegs of rats with unilateral basal ganglia lesions. A kainic acid lesion of one neostriatum reduced tremor intensity in the contralateral leg (CL). Unilateral electrolesions of the globus pallidus and nucleus accumbens had no effects on tremor. Both entopeduncular and subthalamic nuclei lesions reduced the frequency and intensity of tremorine tremor in the CL leg. The subthalamic lesion also increased tremor intensity and frequency in the ipsilateral leg. Lesions were made in some brain areas that receive basal ganglia efferent projections. Peak tremor intensity and frequency in both legs was greatly reduced by unilateral decortication. Unilateral lesions of the habenula, red nucleus and pedunculopontine nucleus had no effects on tremor intensity but reduced peak tremor frequency. Lesions of the substantia nigra and periaqueductal gray area had no effects on tremor. Unilateral removal of the superior colliculus reduced tremor intensity in both legs. The findings suggest that intensity and frequency of tremor are influenced by different basal ganglia efferent pathways; intensity involves strio-entopeduncular-cortical projections and frequency is determined by projections to midbrain and brainstem. The superior colliculus, with many muscarinic receptors, may be a direct target area for tremorine.

Animals↗

Effect of lesioning dopamine, noradrenaline and 5-hydroxytryptamine pathways on tremorine-induced tremor and rigidity.

The effects of lesioning monoamine pathways in the rat brain on tremorine-induced hind-limb tremor and rigidity were studied. Nigro-striatal and mesolimbic dopamine (DA) neurones were lesioned unilaterally by injecting 6-hydroxydopamine (6-OHDA) into the median forebrain bundle. Tremor was reduced in the contralateral leg and rigidity was prevented in the ipsilateral leg. Injection of 6-OHDA into the nucleus accumbens affected tremor but not rigidity. In general, nigral DA neurones may influence rigidity whilst mesolimbic DA neurones affect tremor. A unilateral locus coeruleus electrolesion which destroys noradrenaline (NA) fibres reduced both tremor and rigidity. A median raphe electrolytic lesion affecting 5-hydroxytryptamine (5-HT) neurones had no effect on tremor and rigidity, whereas lesioning the dorsal raphe electrolytically or by injecting 5,6-dihydroxytryptamine prevented rigidity without affecting tremor. Electrical stimulation of the dorsal raphe increased transiently the hindlimb tone of normal rats. The findings demonstrate that the monoamines, especially 5-HT, are differently involved in the mechanisms of tremor and rigidity produced by tremorine.

Animals↗

A method for measuring drug-induced changes in limb muscle tone in the rat.

A method for measuring the time-course and magnitude of changes in rat hind leg muscle tone in vivo is described in detail. The rat is held in a restraining box and the apparatus pushes each hindpaw from behind a distance of 1 cm and measures the force required to briefly hold each leg in the displaced position. The push-relax cycle is repeated every 45 s. Identical measurements were obtained from the 2 hind legs. Experimental results are presented to demonstrate the potential of the technique for investigating the effects of drugs on muscle tone. Morphine, which is known to cause rigidity, increased the force required to displace the hind legs. Muscle tone was reduced in rats that were lightly anaesthetized.

Animals↗

Induction of wet-dog shaking in rats by analogues and metabolites of thyrotrophin-releasing hormone (TRH).

The ability of thyrotrophin-releasing hormone (TRH), its metabolites and several analogues to induce wet-dog shaking (WDS) was tested by their injection into the periaqueductal grey region of male rats. TRH and its metabolite deamido-TRH (TRH-OH) both stimulated WDS, though TRH-OH gave a longer duration of response; other TRH metabolites were inactive. Of the TRH analogues studied, RX77368 (pGlu-His-3,3'-dimethyl-ProNH2) was the most potent in this behavioural test system. Both CG3509 and CG3703 were also very active in inducing WDS, as were their deamidated metabolites. The relative stability of the TRH analogues to enzymic degradation in the brain may be related to their enhanced behavioural activity over TRH. The production from these analogues of biologically-active metabolites may also explain the increased activity in stimulating WDS of the parent peptides.

Animals↗

Decreased bone mineral status in lactating adolescent mothers.

To determine the calcium and bone mineral status of lactating adolescents, we compared 12 lactating adolescents with 11 nonlactating adolescents, 11 lactating adults, and 11 nulliparous adolescent control subjects. At two and 16 weeks, there were no differences in maternal serum concentrations of calcium, phosphorus, alkaline phosphatase, or calcidiol (25-hydroxyvitamin D). The bone mineral content at two weeks among the four groups was not different, but at 16 weeks the lactating adolescents' bone mineral content was lower than that in the other groups. The lactating adolescents' bone mineral content was decreased between two and 16 weeks (1.049 +/- 0.088 vs 0.887 +/- 0.054 gm/cm; P less than 0.02). Dietary intakes were similar among the groups for calories, protein, vitamin D, calcium, and phosphorus. However, only three of ten lactating adolescents met the recommended dietary allowance for calcium or phosphorus (1,600 mg/day), whereas eight of ten nonlactating adolescents, six of seven lactating adults, and seven of ten adolescents control subjects met the recommended dietary allowance for calcium or phosphorus (P less than 0.05). Our data suggest that during 16 weeks of lactation, the adolescent mother may be at risk for bone demineralization because of low dietary intakes of calcium or phosphorus.

25-Hydroxyvitamin D 2↗

Effect of morphine on catecholamine - stimulated cyclic AMP production in cortex slices from rats and mice.

Morphine (10 micro M) blocked noradrenaline-stimulated cyclic AMP production in slices of cerebral cortex from normal rats but not in slices from rats pretreated with 6-hydroxydopamine (6-OHDA). In contrast, morphine failed to prevent noradrenaline-stimulated cyclic AMP production in mouse cortex slices. Levorphanol weakly antagonized the rise in cyclic AMP produced by noradrenaline in both normal and 6-OHDA-treated mouse cortex. Morphine had no effect on the adrenaline-stimulated cyclic AMP accumulation in mouse cortex but it entirely prevented the rise in cyclic AMP produced by isoprenaline. This effect was no observed in brain slices from 6-OHDA-treated mice. It is concluded that in slices of rat cortex, morphine stimulates postulated presynaptic, 6-OHDA-sensitive, opiate receptors associated with noradrenergic nerve terminals. These opiate receptors alter postsynaptic alpha - and beta - adrenoceptor activity. In the mouse, morphine appears to stimulate presynaptic opiate receptors that modify exclusively beta - adrenoceptor-mediated cyclic AMP production.

Animals↗

Role of globus pallidus and substantia nigra efferent pathways in striatally evoked head turning in the rat.

These studies have examined the role of brain areas that receive efferent projections from the globus pallidus (GP) and substantia nigra (SN) in producing the contralateral head turning evoked by unilateral electrical stimulation of the neostriatum in the conscious rat. Two parameters were studied: the latency for a 90 degree head turn and changes in the normal latency evoked by administration of the GABA drugs picrotoxin and muscimol in GP. Electrolesions in the ipsilateral ventromedial and centromedian thalamic nuclei had no effect on the head turn parameters. Although small electrolesions in the SN slowed, but did not abolish the head turn, it prevented the changes in the response latency brought about by GABA drugs in GP. Treatment with 6-hydroxydopamine, which partly destroyed the nigro-striatal dopamine neurones, had no effect on the head turn. Areas of the brainstem that receive basal ganglia efferents were lesioned. An electrolesion of the nucleus tegmenti pedunculopontinus had no effect on the head turn latencies. The head turning was abolished by a lesion in the lateral periaqueductal grey (PAG); a more rostral PAG lesion, on the same level as SN, was ineffective. It is concluded that the head turning is mediated by basal ganglia efferents which pass close to the nigra without synapsing and project to the PAG. The GABA-sensitive GP efferents which modulate the response, probably project to SN.

Animals↗