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Biomedical subjects

K Hole

Publications and source records attributed to K Hole.

At least 109 records · Page 6Linked to original sources
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

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↗
PubMed1981

Does ethanol stimulate brain opiate receptors? Studies on receptor binding and naloxone inhibition of ethanol-induced effects.

The ability of ethanol to stimulate opiate receptors was investigated. Administration of ethanol 2-3.5 g/kg in rats induced analgesia as tested by the tail flick method, reduced body temperature, impaired sensorimotor performance and induced "sleep". Naloxone HCI (0.5-10 mg/kg) did not significantly attenuate these ethanol-induced behavioural changes. [3H]Etorphine binding to opiate receptors in membrane preparations from rat and mouse brains was unchanged by ethanol concentrations of 0.05-3% (v/v). It was concluded that the ethanol effects studied were not mediated by naloxone-sensitive opiate receptors.

Animals↗
PubMed1981

Regulation of pain sensitivity in the central nervous system.

Nociceptive information may be inhibited by stimulation of opiate receptors located presynaptically on primary afferent neurons. Sensory signals entering the spinal cord inhibit nociceptive signals by a non-opioid "gate" mechanism. Descending systems also modulate pain sensitivity at the spinal level. The descending 5-hydroxytryptamine (5-HT) system has a tonic inhibitory function, with diurnal fluctuations in intensity. The strong analgesic effects of electrical stimulation and morphine microinjections in certain brainstem structures is probably mediated by other descending systems. The ascending 5-HT system may influence the results of some complex tests for pain sensitivity by altering e.g. emotionality and habituation rate. Acupuncture analgesia involves opioid systems. In high frequency electroacupuncture and transcutaneous nerve stimulation, a non-opioid "gate" mechanism may predominate. Acute stress may produce analgesia by opioid as well as non-opioid mechanisms. The control of pain sensitivity is influenced by learning (e.g. biofeedback techniques and social factors), and may be affected in depression, mania and schizophrenia.

Animals↗
PubMed1981

Biologically active peptide-containing fractions in schizophrenia and childhood autism.

It is well documented that peptides have a major role in the effective functioning of higher animals at all levels from enzyme stabilization to homeostatic mechanisms governing essential functions such as eating, sexual behavior, and temperature regulation. The effects of exogenously administered peptides on neurotransmitter release, uptake, metabolism and behavioral consequences are also well established. We have attempted to extend these findings by postulating peptidergic neurons as transducers of multisignal inputs, and that development of pathological states may be due to genetically-determined reduced levels of activity of key peptidases, leading to excretion of regulatory peptides into the circulation. We have been able to demonstrate that, in schizophrenia and autism (in well defined clinical cases), the patterns of peptides and associated proteins from urinary samples differ considerably from each other and from normal controls. In addition to this, further purification of the material obtained has led to the discovery of a number of factors capable of modulating the function of major neurotransmitters. Some of these are in the final stages of characterization as peptides, while the remainder are also probably peptides, as purification has been followed by both biological testing and chemical analysis for peptidic material. We have outlined a number of parameters which we consider relevant in any attempt to put psychiatric disorders on a biological foundation. Any new advances in the neurochemical understanding of such disorders must take into consideration the observations of several different disciplines including genetics and psychology. However, at this stage of research it is far too early to speculate on the relevance of the various biological activities to the etiology and symptomatology of schizophrenia and childhood autism.

Autistic Disorder↗
PubMed1980

Nociception is enhanced after low doses and reduced after high doses of the serotonin receptor agonist 5-methoxy-N,N-dimethyltryptamine.

The effects on pain sensitivity of intracerebroventricular injections of 5-methoxy-N,N-dimethyltryptamine were tested by the tail-flick method. Following administration of 1.6, 3.1, 6.3, 12.5 and 25 micrograms (n = 8 for each dose), tail-flick latencies were reduced by 13-24%. Fifty and 100 micrograms caused a biphasic response (hyperalgesia followed by analgesia), whereas 400 micrograms increased mean latencies by 28-39%. The hyperalgesia observed after low doses was most likely due to reduced activity in descending serotonergic neurons following presynaptic stimulation. Higher doses caused analgesia, probably by stimulating spinal postsynaptic serotonergic receptors as well.

Animals↗
PubMed1980

Patterns of peptides and protein-associated-peptide complexes in psychiatric disorders.

Peptidic neurones may be considered as multisignal intergrators and transducers. When formation or release of peptide outstrips genetically determined breakdown capacity, overflow of peptides to the body fluids and urine may be expected. In this paper, pathological urinary chromatographic patterns of peptides are shown for genetic, functional and mixed disorders. Part symptoms of the disorders may be induced with the biologically isolated and purified peptides as well as with chemically synthesized peptides.

Adolescent↗
PubMed1979

A sexually dimorphic rhythm in oestradiol-activated lordosis behaviour in the rat.

Ovariectomized rats exposed to constant plasma levels of oestradiol showed a daily rhythm in lordosis behaviour, with high levels of lordosis occurring during the dark portion of the daily light: darkness cycle and low levels during the light period. Similarly treated male rats failed to show a rhythm in lordosis behaviour. However, neonatal castration permitted the expression of the lordosis rhythm in male rats; conversely, an injection of 1.25 mg testosterone propionate on day 4 of life abolished the rhythm in female rats. Pinealectomy, adrenalectomy or depletion of brain 5-hydroxytryptamine levels did not affect the periodicity in lordosis behaviour but lesions in the suprachiasmatic nuclei of the hypothalamus disrupted the rhythm. It is suggested that the daily rhythm in lordosis behaviour participates in the control of the termination of heat in the female rat and that the perinatal hormone milieu may exert permanent effects on periodic functions.

Animals↗
PubMed1978

Effects of p-chloroamphetamine and 5,7-dihydroxytryptamine on the sexual behavior of gonadectomized male and female rats.

Treatment with the 5-HT neurotoxins p-chloroamphetamine (PCA, 2 X 10 mg/kg) or 5,7-dihydroxytryptamine (5,7-DHT, 2 X 6 microgram intracerebrally) stimulated the display of all aspects of sexual behavior, including ejaculations, by castrated male rats in the absence of testosterone (T) treatment and increased the behavioral sensitivity to a low level of T stimulation. The reduction of the (3H) 5-HT uptake after PCA treatment was more pronounced in the cortex than in the hypothalamus. 5,7-DHT treatment reduced the (3H) 5-HT uptake in the septum, hippocampus, amygdala, hypothalamus and cortex but the behavioral effects produced by the 5,7-DHT treatment could not be correlated to the biochemical effects in any of these brain areas. Since the behavioral effect of PCA appears to be stronger than that of 5,7-DHT, the 5-HT neurotoxins may exert their effect on sexual behavior in forebrain structures rather than in the hypothalamus. PCA treatment had a very small effect on mounting behavior but 5,7-DHT treatment stimulated the display of mounts and intromission patterns by ovariectomized female rats given no hormone treatment. Neither PCA nor 5,7-DHT had any effect on lordosis behavior tested before and after treatment with estradiol benzoate alone or in combination with progesterone. The observations support the conclusion that 5-HT is involved in the control by T of sexual behavior in male rats, but argue against a role of 5-HT in the neural control of lordosis behavior.

5,7-Dihydroxytryptamine↗
PubMed1977

5,7-Dihydroxytryptamine lesions of the ascending 5-hydroxytryptamine pathways: habituation, motor activity and agonistic behavior.

Rats were injected stereotactically in mesencephalon with 5,7-dihydroxytryptamine (5,7-DHT) in the medial 5-hydroxytryptamine (5-HT) pathway (n = 8) and in the medial plus the lateral 5-HT pathways (n = 7) or injected with vehicle (n = 8), or sham-operated (n = 8). The 5,7-DHT lesions reduced the in vitro 3H-5-HT uptake in the hypothalamus and the cortex cerebri to 27-51% of control values, 3H-noradrenaline uptake was not significantly changed. 5,7-DHT lesions of the medial, and of the medial plus the lateral, 5-HT induced mouse killing behavior and increased number of boxing positions in the shock elicited fighting test. Both lesions also reduced the rate of habituation to touch, but only the lesion of the medial plus the lateral 5-HT pathway significantly reduced the rate of habituation to acoustic stimulation. Activity in the home cage was not significantly changed by the lesions. It was concluded that selective chemical lesions of the ascending 5-HT pathways result in prolonged habituation of the orienting response and increase in particular components of agonistic behavior. The increase in locomotor activity observed after electrolytic lesions of nucleus raphe medianus seems not to be due only to lesion of the 5-HT neurons ascending from this nucleus.

5,7-Dihydroxytryptamine↗
PubMed1976

Activity, avoidance learning and regional 5-hydroxytryptamine following intra-brain stem 5,7-dihydroxytryptamine and electrolytic midbrain raphe lesions in the rat.

Rats underwent one of the following treatments: (1) electrocoagulation of both the dorsal and median midbrain raphe nuclei; (2) 5,7-dihydroxytryptamine creatinine sulfate (5,7-DHT) injection (10 mug, as the salt, in 5 mul vehicle) into the vicinity of each midbrain raphe nucleus; (3) intra-brain stem vehicle (5 mul of 0.2% ascorbic acid in isotonic saline) injections; or, (4) a control operation. Open field activity and one-way avoidance conditioning were examined on postoperative days 16-23. Regional central 5-hydroxytryptamine (5-HT) and catecholamine (CA) concentrations were determined 25-27 days postoperatively. Regional 5-HT levels were greatly reduced following 5,7-DHT administration and electrolytic raphe lesions. The 5,7-DHT rats also showed a reduction in spinal 5-HT content. Central CA concentrations were not affected. Variation in the pattern of regional 5-HT changes after 5,7-DHT treatment was observed but appeared to be related to the adequacy of the dorsal raphe (B7) injection. Only the electrolytic raphe lesion animals, however, showed increased locomotor activity and retarded acquisition and forced-extinction of the one-way avoidance response. In contrast, no significant differences were observed in the open field and avoidance behavior of the 5,7-DHT, vehicle, and control groups. The hyperactivity and impaired one-way avoidance performance observed after electrolytic midbrain raphe lesions are not related simply to reductions in regional forebrain 5-HT and may well be due to damage of non-serotonergic neural systems. Clearly, the behavioral effects of central 5-HT depletion depend on the method employed. The role of 5-HT in regulating activity level and mediating avoidance behavior, furthermore, remains to be determined.

Animals↗
PubMed1976

Behavioral effects of 5, 7-dihydroxytryptamine lesions of ascending 5-hydroxytryptamine pathways.

In protriptyline (25 mg/kg) pretreated rats stereotactic 5,7-dihydroxytryptamine (5,7-DHT) lesions of the medial plus laternal 5-hydroxytryptamine (5-HE) bundles in the mesencephalon increased the 5-HT fluorescence in these bundles, and reduced the in vitro uptake of [3H] 5-HT in the hypothalamus to 16% of control values after 2 mug 5,7-DHT/4mul and 12% after 4 mug 5,7-DHT/4mul, and in the cortex cerebri to 35 and 34% of control values, respectively. Selective lesion of the medial 5-HT bundle reduced [3H] 5-HT uptake both in hypothalamus and in cortex cerebri to 45-48% of control values, while selective lesion of the lateral 5-HT bundles significantly reduced [3H] 5-HT uptake only in cortex (to 73-75%). No significant change was observed in [3H] noradreanaline uptake after any injection, or in [3H] 5-HT uptake after vehicle injections. Locomotor activity in an open field 3-10 days postoperatively was significantly reduced by lesions of the medial plus lateral 5-HT bundles. 5-Hdroxytryptophan (50 mg/kg) and a peripheral decarboxylase inhibitor (MK 486, 75 mg/kg) 17 days postoperatively induced a pronounced behavioral "5-HT syndrome" in these rats with medial plus lateral lesions but not in controls. Pain sensitivity, as measured by the hot plate test, was not changed by any lesion, even when tryptophan hydroxylase was partly inhibited with alpha-propyldopacetamide (100 mg/kg). Morphine analgesia and acquisition of a one-way avoidance response also were unchanged. Apomorphine (2 mg/kg)-induced locomotor activity and stereotyped behavior, as measured in an Animex activity meter, were not significantly different from control values in the 5,7-DHT groups. It was concluded that the medial 5-JT BUNDLE INNERVATES BOTH THE HYPOTHALAMUS AND THE CORTEX CEREBRI AND THE LATERAL 5-HT bundle mainly the cortex. These ascending 5-HT neurons are involved in maintaining open field ambulation. No wupport was obtained for the view that they are involved in pain mechanisms, in morphine-induced analgesia, in apomorphine-induced motor behavior, or in one-way avoidance learning.

Afferent Pathways↗