Biomedical subjects

G Curzon

Publications and source records attributed to G Curzon.

At least 91 records · Page 5Linked to original sources

PubMed1986

Effects of clonidine on central and peripheral nerve tone in primary hypertension.

To define the mechanisms whereby clonidine lowers blood pressure, we measured cerebrospinal fluid and plasma levels of norepinephrine, normetanephrine, epinephrine, dopamine, and the dopamine metabolite homovanillic acid in 10 primary hypertensive subjects before and after 3 months of clonidine treatment (mean dose, 0.68 mg/day). Catecholamines were measured by radioenzymatic methods. Cerebrospinal fluid and plasma sampling was performed after subjects had fasted and remained supine overnight, and plasma sampling was repeated 2 hours later, after subjects had ambulated. Supine and upright blood pressure fell, as might be expected. Cerebrospinal fluid levels of norepinephrine and normetanephrine fell significantly, but dopamine and homovanillic acid levels were unchanged. Plasma norepinephrine, normetanephrine, and epinephrine levels decreased 30 to 50%, and supine dopamine levels also fell. The percent fall in supine blood pressure was related to the fall of cerebrospinal fluid and plasma norepinephrine. There were also positive relationships between the decreases of plasma norepinephrine and of normetanephrine and dopamine. The cerebrospinal fluid/plasma norepinephrine ratio was unaffected by clonidine, suggesting that the drug lowered both pools equally. Our findings indicate that clonidine decreases both central and peripheral norepinephrine activity. The dopaminergic activity of cerebrospinal fluid was unaffected by clonidine, and though plasma dopamine levels tended to be lower after treatment, mean plasma prolactin level, an index of dopaminergic activity, was also unchanged. The fall in plasma epinephrine level is probably related to diminished sympathetic adrenomedullary stimulation and is unlikely to contribute to clonidine's antihypertensive action. These results also suggest that measurement of normetanephrine in cerebrospinal fluid and plasma provides a good index of norepinephrine activity.

Adult↗

PubMed1985

Central serotonergic responses and behavioural adaptation to repeated immobilisation: the effect of the corticosterone synthesis inhibitor metyrapone.

Rats were immobilised for 2 h/day. Twenty-four hours after the 1, 3 or 7 immobilisation periods they were injected with the 5HT agonist 5-methoxy-N,N-dimethyltryptamine (5MeODMT; 5 mg/kg i.p.) and behavioural responses (i.e. hind limb abduction, forepaw treading, head weaving, tremor, Straub tail) compared with those of a control group. As we have previously observed after 7 (but not after 1 or 3 immobilisations) forepaw treading and tremor were enhanced and the other responses unaffected. Pretreatment with metyrapone (a corticosterone synthesis inhibitor 150 mg/kg i.p., 3 h before each immobilisation) did not affect the above responses to 1 immobilisation, increased tremor after 3 immobilisations and also increased forepaw treading, hind limb abduction and Straub tail after 7 immobilisations but decreased head weaving under the latter conditions. Metyrapone without immobilisation had no effect on responses to 5MeODMT. Twenty four hours after 1 or 3 (but not 7) immobilisation periods, rats placed for the first time in an open field showed less locomotion and rearing and more defaecation than control animals. Rats also given metyrapone exhibited normal open field behaviour after only 3 immobilisations. The drug also accelerated the return to normal on repeated immobilisation of the impairment of food intake and growth rate which occurred after a single immobilisation. The results as a whole suggest that metyrapone promotes behavioural adaptation to repeated immobilisation and that this is associated with enhanced postsynaptic responses to 5HT. These findings suggest that immobilisation stress-induced changes might be relevant as an animal model for depression which incorporates reported biochemical abnormalities in the illness and is of relevance to proposals concerning its precipitation by stress.

Adaptation, Physiological↗

PubMed1985

Reduced-5-hydroxytryptamine-dependent behavior in rats following chronic corticosterone treatment.

The effect of chronic corticosterone treatment (50 mg/kg s.c. 2 x daily) for up to 4 days on behavioural responses to drugs affecting 5-hydroxytryptamine (5-HT) and dopamine (DA) systems was examined in rats 20 h after the last treatment, when placed in experimental cages, to which they had become habituated. Corticosterone- and vehicle-treated rats exhibited both comparable spontaneous behavior when given 0.9% NaCl i.p. and showed similar behavioural responses following amphetamine (3 mg/kg i.p.). However, responses to the 5-HT-releasing drug p-chloroamphetamine (PCA, 4 mg/kg i.p.) were altered with decreased head-weaving hind-limb abduction and forepaw treading. Postsynaptic changes appear to be involved as responses to the 5-HT agonist 5-methoxy-N,N-dimethyltryptamine (5-MeODMT, 5 mg/kg i.p.) (tremor, hind-limb abduction and forepaw treading) were also decreased. Hind brain and striatal concentration of 5-HT, DA and their metabolites were comparable in corticosterone and vehicle treated rats killed 20 h after the last treatment. Brain PCA levels determined 30 min after injection were also comparable in both groups. PCA induced behaviour was not altered 20 h after 1 day corticosterone treatment or 4 day after 1 day treatment and 5-MeODMT-induced behaviour was not altered 20 h after 14 days treatment with a lower dose of corticosterone (10 mg/kg s.c. x 2). Twenty h after 1 day corticosterone treatment (50 mg/kg s.c. x 2), rats placed in an open field for the first time showed significantly more activity and dropped fewer faecal pellets than controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1985

Enhancement of some 5-HT-dependent behavioural responses following repeated immobilization in rats.

Responses to drugs affecting 5-hydroxytryptamine (5-HT) and dopaminergic (DA) system have been examined in rats after repeated immobilization. Groups of rats were immobilized for 2 h per day for up to 7 days. Twenty-four hours later their behavioural responses to various drugs were tested. Rats immobilized for 7 days showed decreased sniffing and increased grooming and body shakes. When given amphetamine (3 mg/kg, i.p.) the intensity of classical dopamine-dependent behaviours was similar to that of non-immobilized controls. Some responses to the 5-HT releaser p-chloroamphetamine (PCA) (4 and 10 mg/kg, i.p.) and the 5-HT agonist 5-methoxy-N,N-dimethyltryptamine (5-MEODMT) (5 mg/kg, i.p.) (forepaw treading and tremor) were enhanced after 7 days immobilization but others (limb abduction and headweaving) were not. These responses were not enhanced after 1 or 3 days immobilization. Backward walking and body shakes induced by PCA were also enhanced after 7 days immobilization. Concentrations of 5-HT, DA and their metabolites in striatum, cortex, hippocampus, hypothalamus and midbrain of non-drug-treated control and immobilized groups were comparable. Brain PCA concentrations 30 min after injection were also comparable. The above biochemical and behavioural data suggest that repeated immobilization increases some 5-HT postsynaptic functions. These results are discussed in relation to non-drug-provoked behavioural abnormalities occurring 24 h after the first immobilization but no longer evident after 7 periods of immobilization.

Animals↗

PubMed1985

Low doses of the putative serotonin agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) elicit feeding in the rat.

The effects of the putative serotonin agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) on food intake in non-deprived male rats were investigated. Low doses of 8-OH-DPAT (15-60 micrograms/kg) significantly increased food intake, without affecting drinking, grooming, rearing or locomotion. Microstructural analysis of the elicited feeding behaviour revealed that the rate of eating after 8-OH-DPAT treatment was very similar to that previously reported following 16 h food deprivation. Higher drug doses (250-4,000 micrograms/kg) also elicited feeding and caused locomotor stimulation and serotonin-related stereotyped behaviour (i.e. forepaw padding, headweaving, wet dog shakes, flat body posture). When feeding and stereotypy were observed concurrently, response competition was evident and feeding behaviour was fragmented into numerous short eating bouts. As drug-induced stereotypy declined with time, this fragmented pattern of eating was succeeded by long bouts of eating which were similar to those observed at doses of 15-60 micrograms/kg 8-OH-DPAT. The induction of feeding by a serotonin agonist appears paradoxical, since drugs which enhance brain serotonergic activity usually inhibit feeding.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1985

Association between learning and cortical catecholamines in non-drug-treated rats.

Seventeen male Sprague-Dawley rats were trained to eight to nine correct responses on a delayed spatial alternation test performed on alternate days in a T-maze. Locomotor activity in an observation box was scored on 2 consecutive days. The animals were killed 2 weeks after the end of behavioural testing and dopamine (DA), noradrenaline (NA), 5-hydroxytryptamine (5HT), the DA metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) and the 5HT metabolite 5-hydroxyindoleacetic acid (5HIAA) determined in cortex, hippocampus, striatum and hypothalamus. Cortical concentrations of both DA and NA correlated negatively and significantly with the number of errors made in learning the alternation task, though the latter correlation was less striking and became negligible after the correlation between DA and NA was partialled out. Concentrations of DA and NA in the other regions did not correlate significantly with errors. None of the other neurochemical variables correlated significantly with either errors or locomotor activity, except for hypothalamic HVA concentration which showed a marginally significant correlation with locomotor activity. The above results, together with effects of brain lesions reported by other authors, strongly indicate that cortical catecholamines facilitate learning in the normal non-drug-treated rat.

Animals↗

PubMed1985

Characteristics of feeding induced by the serotonin agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT).

The effects of the putative serotonin agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) on food intake in freely-feeding and food deprived rats were examined. In freely-feeding rats, low doses of 8-OH-DPAT (15-60 micrograms/kg) significantly increased food intake without affecting drinking, grooming, rearing or locomotion. Higher drug doses (125-4000 micrograms/kg) also produced feeding and caused locomotor stimulation and serotonin-related stereotyped behaviour (i.e., forepaw padding, headweaving, wet dog shakes, flat body posture). When feeding and stereotypy were observed concurrently, response competition was evident and feeding behaviour was fragmented into numerous short eating bouts. As drug-induced stereotypy declined with time, this fragmented pattern of eating was succeeded by long bouts of eating which were similar to those observed at doses of 15-60 micrograms/kg 8-OH-DPAT. In 24 hr food deprived rats, low doses of 8-OH-DPAT had no effect on food intake. However, high doses of 8-OH-DPAT (250-4000 micrograms/kg) decreased feeding in food deprived animals, an effect which was probably secondary to the induction of stereotypy. It is proposed that the behavioural effects of 8-OH-DPAT may be explained by a dual effect on brain serotonergic mechanisms, which is dose dependent. Thus, low doses of the drug may preferentially activate inhibitory presynaptic serotonin receptors (autoreceptors), decrease serotonin metabolism and thereby increase feeding. In contrast, high doses of 8-OH-DPAT appear to stimulate postsynaptic serotonin receptors and thus produce stereotypy. Alternatively, it is possible that 8-OH-DPAT may elicit feeding by postsynaptic serotonin receptor blockade.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1985

3,4-Dihydroxyphenylethylamine and 5-hydroxytryptamine metabolism in the rat: acidic metabolites in cisternal cerebrospinal fluid before and after giving probenecid.

3,4-Dihydroxyphenylethylamine (DA, dopamine) and 5-hydroxytryptamine (5-HT) turnover values were determined in freely moving male rats by measuring the rates of accumulation of the acidic metabolites of the above transmitters, i.e., 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) in cisternal cerebrospinal fluid (CSF) samples after probenecid (200 mg/kg i.p.) administration. Determinations on samples before and after acid hydrolysis showed that the latter procedure was necessary for DA turnover determination. Thus whereas total (DOPAC + HVA) increased linearly with time after probenecid, free (DOPAC + HVA) did not. This was because the percentage of DOPAC + HVA in conjugated form increased with time. Determinations on a group of 28 rats during the dark (red light) period showed that cisternal amine metabolite concentrations before probenecid injection did not parallel turnover values. This was probably because individual differences in metabolite egress strongly affect the pre-probenecid values. The poor correlations between CSF tryptophan and 5-HT turnover suggested that differences of brain tryptophan concentration were not major determinants of differences of brain 5-HT metabolism within this group of normal rats. Considering that the rats were of similar weight and that the turnover values were all determined at approximately the same time of day, the three- to fourfold ranges of the turnover values are remarkable. The positive correlation between the DA and 5-HT turnovers of individual rats suggests the existence of common effects on DA and 5-HT turnover in normal rats.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1985

Monitoring the effect of a tryptophan load on brain indole metabolism in freely moving rats by simultaneous cerebrospinal fluid sampling and brain dialysis.

Rats were given L-tryptophan, 50 mg/kg i.p., and its concentration in the CNS was monitored in individual freely moving animals using repeated sampling of cisternal CSF and concurrent striatal dialysis. The 5-hydroxytryptamine metabolite 5-hydroxyindoleacetic acid (5-HIAA) was also measured. Results were compared with changes of central tryptophan and 5-HIAA concentrations in brains of rats killed at various times after administration of L-tryptophan, 50 mg/kg i.p. Tryptophan changes in CSF were proportionate to those in whole brain and followed essentially identical time courses. Results for the striatal dialysate and whole striatum also paralleled each other. Similarly, results for 5-HIAA showed proportionality between CSF and brain and between dialysate and striatum. The data obtained were used to determine pharmacokinetic data for individual rats, i.e., areas under curves for both tryptophan and 5-HIAA and half-lives for the decline of tryptophan. Kinetic parameters varied considerably from rat to rat. However, mean half-lives for tryptophan in CSF, brain, dialysate, and striatum were all comparable. Results in general show the value of repeated CSF sampling and intracerebral dialysis for concurrent monitoring of changes of indole metabolism in the whole brain and a specific brain region, respectively. The methods should be suitable for the continuous monitoring of changes of central transmitter metabolism in parallel with observation of behavior following environmental or dietary changes or drug administration. They also should be of use in the investigation of drug kinetics in the CNS.

Animals↗

PubMed1985

Variables influencing the effect of a meal on brain tryptophan.

Previous work from our laboratory points to plasma free tryptophan being a useful predictor of brain tryptophan concentration in many circumstances. Other work, in particular various studies on the acute effects of food intake, has emphasized the roles of plasma total tryptophan and of plasma large neutral amino acids that compete with tryptophan for transport to the brain. We have now studied associations between the above variables under different dietary conditions. Rats were allowed to feed for restricted periods during a 12-h light-12-h dark cycle. In the first study, rats were given access to a carbohydrate diet for 2 h midway through the light cycle and following an 18-h fast. The resultant rise of brain tryptophan was explicable largely by the associated fall in large neutral amino acids. In a second study, rats were adapted to a regimen whereby they were allowed access to the standard laboratory diet for 4 h during the dark cycle for 3 weeks. A postprandial decrease in brain tryptophan was associated with a fall in free tryptophan and of its ratio to competing amino acids. The brain change could be attributed neither to changes in plasma total tryptophan (which increased) nor to changes of its ratio to the competers (which remained unchanged). Results as a whole are thus consistent with changes of plasma free tryptophan and large neutral amino acid concentrations affecting brain tryptophan concentration under different dietary circumstances. It is suggested that these influences serve to maintain brain tryptophan when dietary supplies are defective.

Amino Acids↗

PubMed1984

Effect of alpha-methyl fluorodopa on dopamine metabolites: importance of conjugation and egress.

The effects of D,L-alpha-monofluoromethyldopa (MFMD), an inhibitor of aromatic L-amino acid decarboxylase, on the metabolism of dopamine (DA) and 5-hydroxytryptamine was investigated using rat brain and cerebrospinal fluid (CSF). Vehicle or MFMD (100 mg/kg) was given p.o. and 16 h later probenecid (200 mg/kg i.p.). CSF was sampled and the rats killed immediately or after 1 h. Vehicle treated rats showed regional differences of percentage conjugation of DA metabolites: 3,4-dihydroxyphenylacetic acid (DOPAC), striatum 10%, rest of brain 45%, CSF 67%; homovanillic acid (HVA), striatum 20%, rest of brain 35%, CSF 53%. These differences and the proportionately greater increases of conjugates than of free acids after probenecid vitiate regional comparisons of DA metabolism if conjugates are not included. MFMD alone decreased neither 5HIAA (except in the striatum) nor the free DA metabolites but decreased both conjugates in CSF and conjugated DOPAC in rest of brain. The inhibitory effects of MFMD on 5HT and DA synthesis were most evident when measured by the accumulation of 5HIAA or total (DOPAC + HVA) after giving probenecid. MFMD may also inhibit amine metabolite egress and the conjugation of DOPAC and HVA.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1984

Involvement of dopamine in the antinociceptive response to footshock.

The effects of drugs which alter dopaminergic function on footshock-induced antinociception were studied in the rat. Antinociception due to brief (30 s) footshock was inversely related to dopamine (DA). Thus, it was increased by the DA receptor antagonists pimozide and haloperidol and decreased by the specific D2 dopamine receptor agonist LY 141865, but not by the specific D1 agonist SKF 38393. Although pimozide increased the antinociceptive effect of 30-s shock, it decreased that of 30-min shock. It is suggested that DA may have physiological roles in stress-induced antinociception, and that these may differ according to the duration of stress.

Amphetamine↗

PubMed1984

Analgesia induced by brief or more prolonged stress differs in its dependency on naloxone, 5-hydroxytryptamine and previous testing of analgesia.

Analgesia was determined in rats by a standard procedure in which the time taken to withdraw the tail from water at 51 degrees C was noted. The analgesic responses resulting from footshock applied for 30 sec and 30 min showed marked differences in pharmacological profile and in the dependence on experimental conditions. Thus, analgesia induced by footshock applied for 30 sec was enhanced when 5-HT in the brain was decreased by injection of p-chlorophenylalanine (PCPA), was unaffected by naloxone and was dependent on pre-exposure to the test-procedure for analgesia. In contrast analgesia induced by footshock applied for 30 min was attenuated by injection of PCPA and naloxone but was not dependent on pre-exposure to the analgesia test. It is suggested that the analgesia induced by footshock applied for 30 sec and 30 min reflects distinct mechanisms and that, in the former case, the animal behaves as if the shock occurred as a consequence of its motor response to the noxious heat applied during the pre-shock determination of analgesia.

Analgesia↗

PubMed1984

The effects of lesions produced by 5,7-dihydroxytryptamine on 5-hydroxytryptamine-mediated behaviour induced by amphetamine in large doses in the rat.

The role of 5-hydroxytryptamine (5-HT)-containing terminals in the spinal cord and basal ganglia in behavioural responses induced by amphetamine in large doses have been investigated using the neurotoxin for 5-HT, 5,7-dihydroxytryptamine (5,7-DHT). The effects of pretreatment with 5,7-DHT were also examined using the 5-HT agonist, 5-methoxy-N,N-dimethyltryptamine (5-MeODMT). d-Amphetamine (25 mg/kg) induced several classical 5-HT-dependent behavioural responses (head weaving , forepaw treading, hind limb abduction, "wet dog" shakes, Straub tail), together with some classical dopamine (DA)-dependent behaviour and backward locomotion which requires both transmitters. Pretreatment with 5,7-DHT, given into the striatum significantly decreased "wet dog" shakes and virtually abolished backward walking. Pretreatment with 5,7-DHT in the nucleus accumbens or substantia nigra did not significantly alter behaviour. Pretreatment with 5,7-DHT intraspinally did not significantly alter behaviour induced by amphetamine, although a decrease of Straub tail just failed to reach significance (P = 0.056). Similar pretreatment in rats given 5-MeODMT (8 mg/kg) significantly enhanced both Straub tail and tremor but did not alter the other behavioural responses induced by this drug (limb abduction, forepaw treading, head weaving ). The results in general suggest that behavioural responses induced by 5-HT can be classified into 3 groups (a) those requiring striatal 5-HT ("wet dog" shakes and backward locomotion), (b) those requiring spinal 5-HT (Straub tail, tremor) and (c) those requiring neither spinal nor striatal 5-HT (hind limb abduction, head weaving and forepaw treading).

5,7-Dihydroxytryptamine↗

PubMed1984

Concurrent determination of brain dopamine and 5-hydroxytryptamine turnovers in individual freely moving rats using repeated sampling of cerebrospinal fluid.

5-Hydroxytryptamine (5-HT) turnover and dopamine (DA) turnover values were obtained in individual conscious rats by measuring the rates of accumulation of 5-hydroxyindoleacetic acid (5-HIAA), 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) in cisternal CSF samples taken from each rat at 0, 30, and 60 min after probenecid (200 mg/kg i.p.) administration. In a separate experiment, 5-HT and DA turnover values were determined in CSF, striatum, and rest of brain of groups of rats killed 0, 30, or 60 min after probenecid. Whole brain turnover values were calculated from striatal and rest of brain values. Mean turnover values using CSF were comparable with both procedures. DA turnover values were greater when based on total (i.e., free + conjugated) DA metabolites than when based on free metabolites. After partial inhibition of monoamine synthesis with the decarboxylase inhibitor DL-alpha- monofluoromethyl -DOPA ( MFMD , 100 mg/kg p.o.) DA and 5-HT turnover values were comparably reduced in whole brain, rest of brain, and CSF but more markedly reduced in the striatum. Mean DA and 5-HT turnover values obtained using CSF were similar with probenecid doses over the range 150-250 mg/kg i.p. but were variable when repeatedly determined in the same rats after administration of 200 mg/kg probenecid. Results in general show that the CSF procedure may be used to determine concurrently both 5-HT and DA turnover (when estimated from the sum of total but not free metabolites) and that it provides a good index of whole brain turnover of these transmitters in the conscious individual rat.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1984

Determination of daily variations of brain 5-hydroxytryptamine and dopamine turnovers and of the clearance of their acidic metabolites in conscious rats by repeated sampling of cerebrospinal fluid.

Central 5-hydroxytryptamine (5-HT) and dopamine (DA) turnovers were estimated simultaneously in conscious freely moving rats kept on a 12-h dark/12-h light cycle by sampling cisternal CSF of each animal before and after giving probenecid and determining the accumulation of the acidic metabolites of the two amines. The turnovers of both transmitters and the clearances of their acid metabolites from the brain were shown to be significantly greater during the dark (red light) period than during the white light period.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1984

A technique for repeated sampling of cerebrospinal fluid in freely moving rats and its uses.

The CSF plays an important role in removing transmitter amine metabolites from the brain and their measurement therein has frequently been used to study transmitter amine metabolism in the human brain during life. Much data, albeit largely qualitative, indicates that brain transmitter metabolism is reflected in the CSF. There is however remarkably little quantitative data available as human CSF and brain material are rarely concurrently available from the same patient. Conversely, until recently we have had much direct information on transmitter metabolism in the rat brain but CSF studies have been few, largely because of technical difficulties in measuring the metabolites. Therefore we have had little quantitative data on brain--CSF relationships for transmitter amine metabolism in any one species. Such evidence is important not only because it sheds light on the relevance of human CSF findings to brain chemistry but also because it may be used to study transmitter metabolism in the brain of the living rat and provides quantitative data on the role of the CSF in the removal of the metabolites from the brain. We will be reporting findings on these topics. These were obtained by the withdrawal of small volumes of cisternal CSF from conscious freely moving rats via an indwelling catheter and determining dopamine and 5-hydroxytryptamine metabolites by HPLC in both CSF and brain with and without administration of various drugs.

Animals↗

PubMed1983

Analgesia induced by brief footshock: blockade by fenfluramine and 5-methoxy-N,N-dimethyltryptamine and prevention of blockade by 5-HT antagonists.

Analgesia induced by footshock (2 mA, 30 s) is decreased by the 5-HT releaser, fenfluramine, and the rapidly acting 5-HT agonist, 5-methoxy-N,N-dimethyltryptamine (5-MeODMT). These decreases are blocked by the 5-HT antagonists, cyproheptadine and methiothepin. However, the antagonists when given alone do not influence shock-induced analgesia. Therefore, analgesia induced by brief footshock in the absence of drugs may not involve 5-HT-dependent mechanisms even though it may be influenced by pharmacologically provoked changes of 5-HT release or by 5-MeODMT. This drug was also able to attenuate the analgesia after its induction, possibly reflecting a disruption of memory processes rather than of nociceptive mechanisms per se.

Animals↗