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Biomedical subjects

P Redgrave

Publications and source records attributed to P Redgrave.

98 records · Page 6Linked to original sources

Neuroleptic suppression of feeding and oral stereotypy following microinjections of carbachol into substantia nigra.

A large dose of carbachol (5 micrograms/0.5 microliters) unilaterally microinjected into the rostral substantia nigra of rats induced stereotypy characterized by biting, gnawing and licking. A lower dose (0.5 micrograms/0.5 microliter) of the cholinomimetic potentiated normal food intake in satiated animals. Both the cholinergically induced feeding and stereotypy were severely attenuated by subcutaneous administration of haloperidol 0.4 mg/kg. This particular dose of neuroleptic had no significant effect on locomotor activity. These data are consistent with the hypothesis that cholinergic neurotransmission in the rostral substantia nigra mediating oral responses is afferent to the dopamine systems arising from this area.

Acetylcholine↗

Loss of beta-adrenoceptor binding sites in rat striatum following kainic acid lesions.

Intrastriatal injection of kainic acid (5 nmoles) to rats led to severe destruction of nerve cell bodies throughout the caudate-putamen complex and an extensive proliferation of glial cells. Lesioned striata displayed a significant 23% loss of beta-adrenoceptor binding sites 21--24 days after injection of kainic acid. Further analysis of these changes revealed that this loss of sites was selectively within the beta 1 receptor population. Although these results do not rule out a partial glial cell localisation for beta-adrenoceptors, they do indicate that at least a proportion of beta 1 receptors are present on striatal perikarya.

Animals↗

Modulation of intracranial self-stimulation behaviour by local perfusions of dopamine, noradrenaline and serotonin within the caudate nucleus and nucleus accumbens.

In order to examine the possible role of dopamine (DA), noradrenaline (NA) and 5-hydroxytryptamine (5-HT) in the control of intracranial self-stimulation behaviour (ICSS) a push-pull perfusion system was used to administer different consecutive doses of DA, NA and 5-HT to discrete regions within the caudate nucleus (CN) and nucleus accumbens (NAC) of rats during ICSS. Electrode placements supporting ICSS were in both the medial forebrain bundle (MFB) and the ventral mesencephalic tegmentum (VMT). Animals were allowed to determine the ICSS pulse train duration thereby permitting three measures of ICSS behaviour: (1) mean presses/min; (2) mean duration/press and (3) mean time pressed/min. Eleven electrode/cannula combinations were found to be responsive to both DA and 5-HT. The DA response profile was typified by a significant increase in mean presses/min, a significant decrease in mean duration/press and no significant change in the mean time pressed/min. The response profile for 5-HT was the converse of the DA pattern for the first two measures of ICSS, however, again there was no significant change in the mean time pressed/min. In addition, 8 electrode/cannula combinations were sensitive to NA; for 5 combinations the response pattern was similar to that of DA, however, the changes in ICSS were generally larger and of longer duration. For the remaining 3 combinations sensitive to NA there was no major change in mean presses/min but a dramatic increase in the mean duration/press and consequently, an increase in the mean time pressed/min. It is suggested that the central control of ICSS behaviour might depend, in part, upon a relative balance between DA and 5-HT systems within the CN and NAC. The operational characteristics of this balance may be subject to additional modulation by the activation of an adrenergic receptor.

Animals↗

A modified push-pull system for the localised perfusion of brain tissue.

A method for monitoring the outflow of a push-pull perfusion system is presented. This modification possesses the following important advantages: (1) Inadvertent induction of expansion lesions is avoided, (2) Flow rates can be reduced from the usual 50-200 microliter/min to 0.6-1.7 microliter without decreasing the probability of detecting occlusions, (3) Incidence of occlusions is reduced, (4) Up to 30--40 perfusions can be performed at each of several sites in the brain of a single animal over a period of several months. The modified system has been used successfully to administer neurohumoral agents to the brain of rats and to determine the release of endogenous substances into the perfusate.

Animals↗

Hypothalamic Na+ and Ca++ ions and temperature set-point: new mechanisms of action of a central or peripheral thermal challenge and intrahypothalamic 5-HT, NE, PGEi and pyrogen.

The effects of changes in ambient and central temperature, amines, PGEu and pyrogen were investigated with respect to the mechanism of Na+-Ca++ ratio in the posterior hypothalamus of the unrestrained cat. Guide tubes were implanted bilaterally above the posterior hypothalamic area of 23 cats so as to accommodate push-pull cannulae. After a Na+ or Ca++ sensitive site was identified by perfusion at 50 mul/min of an artificial CSF containing 10.4 mM excess Ca++ ions or 13.6 mM excess Na+ ions, several types of experiments were undertaken with the results summarized as follows: if the cat was exposed to a cold or warm environmental temperature as the posterior hypothalamus was perfused with excess cation, the typical hypothermia was produced by Ca++ and hyperthermia by Na+ ions. However, if the cat was exposed to peripheral cooling or warming 30 min prior to the perfusion, the fall or rise produced by Ca++ or Na+ was attenuated or prevented. In other experiments, 1.0 muCi 45Ca++ was injected in the ion sensitive site in the posterior hypothalamus to label stores of the cation. Raising of ambient temperature caused a retention of 45Ca++ in this hypothalmic area, whereas a cold environmental temperature enhanced the efflux of 45Ca++ at the same perfusion site. The magnitude of change in 45Ca++ efflux depended upon the intensity of the thermal challenge. Similarly, warming of the anterior hypothalmic, preoptic area by means of implanted thermodes caused an immediate diminution in 45Ca++ efflux in the posterior hypothalamus, whereas cooling of this anterior region augmented the extrusion of 45Ca++ ions from the posterior area. When substances which produce a temperature change were applied to the same thermosensitive zone, the direction of shift in 45Ca++ flux in the posterior area corresponded to the signal for heat production or heat loss. That is, the microinjection of 5-HT, PGE1 or Salmonella typhosa into the anterior hypothalamus enhanced the efflux of 45Ca++ in the posterior hypothalamus as hyperthermia developed, whereas a similar microinjection of norepinephrine reduced the 45Ca++ output from the same sites. Finally, locally anesthetizing the cells of the anterior hypothalamus by the nerve blocker, procaine, prevented the cold and heat-induced 45Ca++ eflux and retention, respectively. These results suggest that if the Na+-Ca++ ratio in the posterior hypothalamus establishes and maintains the set-point for body temperature of 37 degrees -38 degrees C, the mechanism of lability of Ca++ through changes in binding characteristics, transport, or metabolism of the cation serves two purposes: (1) the active defense of the set-point temperature through gradations in ion shifts; and (2) the upward or downward change in set-point value, pathological or normal, triggered by virtue of impulses relayed from the anterior hypothalamus.

Animals↗