Pharmacologic actions of capsaicin: apparent involvement of substance P and serotonin.
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Biomedical subjects
Publications and source records attributed to G F Gebhart.
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The interaction between chlordiazepoxide (CDP) and forebrain noradrenaline (NA) was investigated in rats with bilateral radiofrequency lesions of the noradrenergic dorsal tegmental bundle (DTB). Forebrain NA was reduced to 35% of control by the DTB lesions; hypothalamic NA and dopamine were unchanged. Rats were trained on a straight alley runway task for food reward. During extinction of the runway task, CDP significantly increased extinction responding in sham lesion animals but not in DTB lesion animals. Thus, CDP was ineffective in increasing resistance to extinction responding in the runway task in animals with significant depletion of forebrain NA.
Rats were trained on an appetitive discretetrial discriminated-punishment task in which they learned to suppress responding when an intense flashing light predicting punishment was present and to respond rapidly on trials when the flashing light was absent. Once animals were performing discriminatively, 0.75, 3.0, or 6.0 mg/kg of morphine (base) was administered and a fear extinction session consisting of 60 nonshocked presentations of the flashing light was given. Two saline control groups, one that received fear extinction and one that did not, were also included in the experiment. On the day following fear extinction, all rats were tested in the undrugged state on the discriminated punishment problem, but without shock. The rats receiving 3.0 and 6.0 mg/kg of morphine before the fear extinction session were suppressed by the flashing light more than the saline extinction group or the 0.75 mg/kg morphine treatment group. Moreover, the two higher dose morphine groups were suppressed as readily as the saline group that received no fear extinction. These results are attributed to the antiemotionality effects of morphine.
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Experiments were carried out in rats to (1) elaborate upon the sepcificity of drug action in the periaqueductal gray matter (PAG), and (2) to evaluate the posible congruence of PAG sites of morphine-induced and stimulation-produced analgesis (SPA) applied at virtually identical PAG loci. It was demonstrated that the effect of morphine intracerebrally (i,c.) administered into the PAG was not duplicated by other centrally acting agents (chlorpromazine, chlordiazepoxide, pentobarbital or naloxone) administered i.c. at the same PAG site. This selective action of morphine in the PAG was further demonstrated not to be test-bound since morphine significantly altered responding in all four of the analgesiometric tests employed. Thus, multiple i.c. injections of drugs at the same PAG locus were useful in demonstrating site specificity of drug action where behavioral and electroencephalographic methods alone had previously provided ambiguous information. Morphine-induced analgesia and SPA, evaluated at virtually coincident PAG sites, revealed only a general congruence of efficacious loci. The most effective PAG loci for morphine-induced analgesia were not the same as those for SPA; analgesia effected by one analgesia-producing manipulation did not reliably predict that analgesia would also be produced by the other analgesia-producing manipulation at the PAG sites examined. In general, the more efficacious analgesia-producing PAG loci were localized in the ventral-ventrolateral PAG.
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Experiments were performed to evaluate the effects on the levels of aspartate, GABA and glutamate in the periaqueductal central gray matter, hypothalamus, midbrain reticular formation and cortex of mouse brain following various treatments. The results indicate that only glutamate among the 3 neurohumors is systematically altered relative to the experimental manipulations. Moreover, among the 4 brain areas examined, the data implicate only the periaqueductal central gray matter as a locus of morphine's antinociceptive action. Morphine also appears to produce a drug-specific effect in hypothalamus which, however, is not analgesia-related. There were no significant pain, stress or drug-related effects on the levels of glutamate in either the midbrain reticular formation or the cortex.
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An electrolytic approach to cutting small-diameter stainless steel tubing is described. The method is superior to abrasion or manual methods because it produces a clear lumen in the smallest diameter tubing available. The method is simple, quick, and inexpensive and has been found valuable for making small injection needles, small tissue punches, and for repairing broken or occluded microliter syringes.