Evidence for selective serotonergic receptor involvement in p-chloroamphetamine-induced antinociception

Ögren, Sven Ove; Berge, Odd‐Geir

doi:10.1007/bf00501202

Cited by 12 publications

(2 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The reduced analgesic effect of PCA may have been caused by the down-regulation of 5-HTz receptors which occurs following chronic treatment with metergoline (Blackshear et al 1983). However, it is not known for certain what type of receptor that mediates the analgesic effect of PCA (Ogren and Berge 1985). This finding is also compatible with the contention that metergoline may act as an agonist at postsynaptic serotonergic receptors.…”

Section: Discussionsupporting

confidence: 84%

Development of tolerance to the antinociceptive effect of metergoline

1987

Self Cite

View full text Add to dashboard Cite

Metergoline given IP reduced the response to noxious stimulation in the mouse formalin test. Tolerance to this effect developed after a chronic treatment schedule consisting of ten daily injections of 5 mg/kg. Twenty four hours after the last injection a test dose of metergoline (2.5 mg/kg) reduced the licking time in the formalin test by 28% in the chronic metergoline group, compared to 68% reduction in the vehicle-treated animals. In addition, the antinociceptive effect of the 5-hydroxytryptamine releasing compound p-chloramphetamine (PCA) was reduced following chronic treatment with metergoline. The reduced effect of PCA may have been caused by down-regulation of 5-HT2 receptors. However, this finding is also compatible with the contention that metergoline may act as an agonist at postsynaptic serotonergic receptors.

show abstract

Section: Discussionsupporting

confidence: 84%

Development of tolerance to the antinociceptive effect of metergoline

1987

Self Cite

View full text Add to dashboard Cite

show abstract

“…The putative 5-HT receptor antagonist metitepin (Jacoby et al, 1975;Monachon et al, 1972;Nelson et al, 1979;Tebecis, 1972) was employed in this study. Metitepin is the most potent blocker of analgesia induced by the 5-HT releasing compound PCA in rats (Ogren and Berge, 1985). The antinociceptive effect of this drug was enhanced in mice with PCA-induced neurotoxic lesions of supraspinal 5-HT systems whereas the actions of 5-HT agonists were unaltered (Eide et al, 1987 b).…”

Section: Introductionmentioning

confidence: 98%

Mechanisms by which the putative serotonin receptor antagonist metitepin alters nociception in mice

Eide

Hole

Berge

1988

J. Neural Transmission

Self Cite

View full text Add to dashboard Cite

The putative serotonin (5-HT) receptor antagonist metitepin (0.5 mg/kg, intraperitoneally) produced hypoalgesia in the increasing temperature hot-plate test and hyperalgesia in the tail-flick test in mice. The effects of metitepin were not altered after depletion of 5-HT by the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT, 80 micrograms free base, intracerebroventricularly) or the serotonin synthesis inhibitor p-chlorophenylalanine (PCPA, 400 mg/kg for 10 consecutive days). After chronic administration (2 or 5 mg/kg for 18 consecutive days) tolerance to the effect of metitepin (0.5 mg/kg) and cross-tolerance to the antinociceptive effect of the 5-HT agonist 5-methoxy-N,N-dimethyltryptamine (5-MeODMT, 3 mg/kg) was found in the hot-plate test but not in the tail-flick test. It is suggested that metitepin may block descending 5-HT transmission while more complex mechanisms of action are involved at supraspinal level. One possibility is that metitepin exhibits partial agonist properties or, alternatively, that the drug may block 5-HT subsystems which tonically enhance nociception.

show abstract

Separation of the associative and non-associative effects of brain serotonin released by p-chloroamphetamine: Dissociable serotoninergic involvement in avoidance learning, pain and motor function

Ögren

Johansson

1985

Psychopharmacology

View full text Add to dashboard Cite

p-Chloramphetamine (PCA, 0.63-5 mg/kg IP) injected 30-60 min before testing produced a dose-related impairment of avoidance acquisition, prolonged reaction time in the hot-plate test and increased locomotor activity. Pretreatment with the selective serotonin (5-HT) uptake inhibitor zimeldine (10 mg/kg IP) blocked these behavioral effects. Degeneration of brain 5-HT neurons by a high neurotoxic dose of PCA (2 X 10 mg/kg IP) or inhibition of tryptophan hydroxylase by p-chlorophenylalanine (300 mg/kg IP) also blocked the behavioral effects of PCA. There was a complete blockade of the PCA-induced avoidance deficit following pretreatment with metergoline, a central 5-HT receptor blocking agent. On the other hand, metergoline failed to block the hot-plate analgesia and the increased locomotion caused by PCA. Depletion of brain NA and DA by the tyrosine hydroxylase inhibitor H44/68 did not counteract the PCA effect on avoidance or hot-plate performance, but reduced the locomotor stimulating effect. The selective NA neurotoxin DSP4 (50 mg/kg IP) or the opiate antagonist naloxone (1 mg/kg) failed to affect the PCA-induced modulations of the behaviours studied. In addition, PCA administration in doses that caused avoidance deficits, did not result in motor impairment as assessed by the tread mill test. The above results support the hypothesis that the PCA-induced impairment of active avoidance acquisition does not involve changes in nociception or altered locomotor activity. It is concluded that behavioural processes related to serotonergic neurotransmission can be independently modified, suggesting differences in the underlying 5-HT mechanisms.

show abstract

Evidence for selective serotonergic receptor involvement in p-chloroamphetamine-induced antinociception

Cited by 12 publications

References 39 publications

Development of tolerance to the antinociceptive effect of metergoline

Development of tolerance to the antinociceptive effect of metergoline

Mechanisms by which the putative serotonin receptor antagonist metitepin alters nociception in mice

Separation of the associative and non-associative effects of brain serotonin released by p-chloroamphetamine: Dissociable serotoninergic involvement in avoidance learning, pain and motor function

Contact Info

Product

Resources

About