Biomedical subjects

O B Fasmer

Publications and source records attributed to O B Fasmer.

27 records · Page 2Linked to original sources

PubMed1985

Selective neurotoxic lesions of descending serotonergic and noradrenergic pathways in the rat.

The ability of neurotoxic substances to induce selective lesions of the descending monoaminergic pathways in rats was investigated. Saline, 6-hydroxydopamine, 5,6-dihydroxytryptamine, or 5,7-dihydroxytryptamine were administered into the lumbar subarachnoid space through a chronically indwelling catheter. The lesions were evaluated 2-3 weeks later by in vitro uptake of [3H]noradrenaline and [14C]5-hydroxytryptamine into synaptosomal preparations from the frontal cortex, brainstem, cervical spinal cord, and lumbar spinal cord of each animal. There was no difference in uptake between saline-injected and noncatheterized controls and no significant changes in cortical uptake after any of the treatments (dose range of neurotoxins: 0.6-80 micrograms). In the lumbar spinal cord, 6-hydroxydopamine (5-80 micrograms) reduced the [3H]noradrenaline uptake by approximately 90% with no effects on [14C]5-hydroxytryptamine uptake, whereas 5,6-dihydroxytryptamine reduced the uptake of [14C]5-hydroxytryptamine by 90% (20-80 micrograms). [3H]Noradrenaline uptake was unaffected by lower doses of 5,6-dihydroxytryptamine but fell by 45-55% after 40-80 micrograms. 5,7-Dihydroxytryptamine (10-80 micrograms) reduced [3H]noradrenaline uptake by 90-95% and [14C]5-hydroxytryptamine uptake by approximately 80% (5-80 micrograms) in the lumbar cord. It is concluded that intrathecal administration of suitable doses of neurotoxins may produce extensive selective lesions of descending noradrenergic and serotonergic pathways.

5,6-Dihydroxytryptamine↗

PubMed1985

Test-dependent antinociceptive effect of spinal serotonin release induced by intrathecal p-chloroamphetamine in mice.

The effect of direct intrathecal injection of p-chloroamphetamine (PCA) into the lumbar subarachnoid space was investigated in mice. PCA (0.6 - 20 micrograms) induced a dose-related prolongation of response latencies in the tail-flick test, but failed to affect the hind-paw lick response in a hot-plate test employing slowly rising temperature. PCA (5 micrograms) given intracerebroventricularly did, however, significantly elevate the response temperature in the hot-plate test. The antinociceptive effect of PCA in the tail-flick test was prevented by spinalization, by pretreatment with the selective serotonergic re-uptake blocker zimelidine (20 mg X kg-1 i.p.) and by the serotonin synthesis inhibitor p-chlorophenylalanine (300 + 300 + 150 mg X kg-1 i.p. 72, 48 and 24 h before test). It is concluded that PCA given intrathecally releases serotonin from spinal terminals, which may under certain conditions induce antinociception.

Amphetamines↗

PubMed1984

Metergoline elevates or reduces nociceptive thresholds in mice depending on test method and route of administration.

Intrathecal injection of metergoline reduced the response latencies in the tail-flick and hot-plate tests, supporting the contention that descending 5-hydroxytryptamine (5-HT) pathways tonically inhibit pain sensitivity. Elevated latencies were, however, observed after both intraperitoneal (IP) and intracerebroventricular (ICV) injections in the hot-plate test, when hindpaw lick was used as the response criterion. These findings may indicate that supraspinal 5-HT pathways tonically increase pain responsiveness in certain test situations . Alternative hypotheses are that metergoline in supraspinal structures acts as an agonist at post-synaptic 5-HT receptors mediating antinociception, or as an antagonist at pre-synaptic 5-HT receptors. Recording of first reaction latencies on the hot-plate showed increased thresholds after IP, but not after ICV injections. This may indicate an action on 5-HT receptors in the brain not accessible after ICV injections, or that the effect is mediated by blockade of peripheral 5-HT receptors.

Animals↗

PubMed1984

Immobilization-induced analgesia: possible involvement of a non-opioid circulating substance.

Stress induced analgesia (SIA) and stress-induced changes in body temperature were studied in mice and rats. Immobilization was used as the stressor. Nociception was measured with the tail-flick method and body temperature was recorded in the colon. Within 5 min of immobilization a similar increase in tail-flick latencies was observed in the two species. Concomitantly, the body temperature increased in the rats and decreased in the mice. Transection of the spinal cord 7 days before the experiments tended to increase the effect of stress on the tail-flick latencies in both species. Pretreatment with naloxone HCL (2 mg/kg SC, 5 min before immobilization) did not influence SIA in either intact or spinal rats. Thus, analgesia induced by immobilization may be due to a non-opioid substance acting peripherally or reaching the spinal cord via the systemic circulation.

Analgesia↗

PubMed1983

Changes in nociception after intrathecal administration of 5,6-dihydroxytryptamine in mice.

Intrathecal administration of 5,6-dihydroxytryptamine (5,6-DHT) (5 micrograms) to mice selectively lesioned descending serotonergic pathways, reducing spinal levels of 5-hydroxytryptamine (5-HT) by 80%, without significantly changing the levels of noradrenaline. Increased sensitivity to noxious stimulation, as measured by the tail-flick and hot-plate tests, was observed 2 days after injection of 5,6-DHT. The tail-flick latencies returned to normal on day 6, but were again reduced by administration of the 5-HT receptor blocker metergoline, suggesting that the normalization process involved compensatory mechanisms in the remaining 5-HT system. In the hot-plate test, the latencies both to shaking or kicking of a hindpaw (kick) and to hindpaw lick were recorded, but the time course for the changes of these two responses was found to be different. The latencies to hindpaw lick were normalized within 2 weeks, whereas the hindpaw kick latencies remained reduced throughout the 21 day observation period.

5,6-Dihydroxytryptamine↗

PubMed1983

Similar behavioural effects of 5-hydroxytryptamine and substance P injected intrathecally in mice.

Intrathecal injection of 5-hydroxytryptamine (5-HT) or of substance P in mice elicited a behavioural syndrome consisting of reciprocal hindlimb scratching and biting or licking, directed towards the caudal parts of the body. 5-Hydroxtryptamine elicited more scratching than did substance P, which in turn caused a greater number of biting or licking responses. The 5-HT-induced responses were mimicked by 5,6-dihydroxytryptamine and inhibited by the 5-HT receptor blocker metergoline. The present findings indicate that 5-HT, injected intrathecally, may have similar effects as substance P in stimulating sensory pathways in the spinal cord.

5,6-Dihydroxytryptamine↗

PubMed1983

Behavioural responses induced by intrathecal injection of 5-hydroxytryptamine in mice are inhibited by a substance P antagonist, D-Pro2, D-Trp7,9-substance P.

Intrathecal injection of 5-hydroxytryptamine (5-HT) in mice produced a behavioural syndrome consisting of reciprocal hindlimb scratching and biting or licking of the hindquarters. Pretreatment with either metergoline or morphine given intrathecally inhibited the 5-HT-induced behaviour. The response to 5-HT was similar to the effect of substance P (SP), and it was found that the blocker of the substance P receptor, D-Pro2, D-Trp7,9-SP, not only reduced the effect of substance P, but also that of 5-HT. The behaviour induced by substance P was also significantly reduced by intrathecal injection of either morphine or metergoline. These findings indicate a functional interaction between substance P and 5-HT in the modulation of sensory input at the spinal level.

Animals↗

PubMed1983

Serotonin receptor antagonists induce hyperalgesia without preventing morphine antinociception.

5-Hydroxytryptamine (5-HT) receptor blockade by administration of mianserin (1 mg/kg) or metergoline (0.25 mg/kg) shortened the response latencies of rats in the hot-plate (hind-paw lick response) and tail-flick tests, but did not consistently attenuate the antinociceptive effect of morphine (1.25--5.0 mg/kg). Injection of the opiate receptor antagonist naloxone (1 mg/kg) did not change tail-flick response latencies and did not interfere with the antinociceptive action of the 5-HT receptor agonist 5-methoxy-N,N-dimethyltryptamine (5-MeODMT). The antinociceptive effect of morphine was reduced in chronically spinal rats, although significant increases in tail-flick latencies were observed after 2.5 and 5.0 mg/kg. Concomitant administration of 5-MeODMT failed to restore the effect of morphine in spinal rats. In the hot-plate test, morphine did not reliably prolong latencies to forepaw lick, indicating that this response is not a useful measure of pain sensitivity. The results suggest that different mechanisms underlie the analgesia induced by systemic administration of morphine and 5-HT mediated tonic inhibition of nociception.

Analgesics↗

PubMed1983

Time course of changes in nociception after 5,6-dihydroxytryptamine lesions of descending 5-HT pathways.

Intrathecal injection of 5,6-dihydroxytryptamine (5,6-DHT) in rats produced selective lesions of the descending 5-HT pathways. Spinal 5-HT levels gradually fell to less than 10% of controls within 10 days of 5,6-DHT administration with no recovery evident within 4 weeks. The uptake of 14C-5-HT into crude spinal synaptosomes was similarly reduced. The uptake of 3H-NA into spinal synaptosomes was unaffected, as was the uptake of 14C-5-HT and 3H-NA into cortical synaptosomes. Following 5,6-DHT, tail-flick latencies were reduced by 20-30% during the first post-injection week, but returned to control levels during the second week. Intrathecal or systemic administration of the 5-HT receptor antagonist metergoline significantly reduced latencies of normal rats and of 5,6-DHT treated rats tested after the second week when the response was normalized. Metergoline did not, however, further reduce the latencies of lesioned rats during the first post-injection week. It is concluded that functional adaptation involving 5-HT neurotransmission compensated for the selective lesion of descending 5-HT pathways induced by 5,6-DHT.

5,6-Dihydroxytryptamine↗