Pharmacological studies on stimulation-produced analgesia in mice

European Journal of Pharmacology
W R Buckett

Abstract

Stimulation-produced analgesia (ESPA) was induced in mice by peripheral caudal electrostimulation and subsequently monitored on a 52 degrees C hot plate. The effects on ESPA of compounds modulating some neurotransmitter systems were studied at appropriate premedication times and at doses at which the compounds themselves did not exhibit antinociceptive actions. The manipulation of catecholaminergic, dopaminergic or GABAergic systems did not modify ESPA. It could be potentiated by an increase in serotoninergic activity following 5-hydroxy-D,L-tryptophan (80-120 mg/kg) and reduced, under certain circumstances, by serotonin depletion with p-chlorophenylalanine (3 x 132 mg/kg). However the serotonin reuptake inhibitors fluoxetine (5 mg/kg) and zimelidine (10 mg/kg) were without effect indicating a complex modulating role of the monoamine. As with morphine-tolerant mice, the induction of ESPA in mice tolerant to methadone and to meperidine has been demonstrated, while the analgesia was not enhanced by chronic naloxone treatment. Although the naloxone reversibility of ESPA has been confirmed, a second acute dose of naloxone (1 mg/kg) did not reverse the analgesia. ESPA could also be fully elicited in adrenalectomized mice. It is conc...Continue Reading

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