The Involvement of Serotonin and Norepinephrine in Opiate Analgesia in the Mouse
Fowler, Adele R.
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The present study investigated the involvement of the neurotransmitters, serotonin and norepinephrine, in opiate analgesia in mice. This was done through the use of agonists selective for each opiate receptor subtype and serotonin and norepinephrine re-uptake blockade to increase the amount of monoamine in the synapse. Mice were pretreated with the selective serotonin re-uptake blocker, zimelidine or the selective norepinephrine re-uptake blocker, desipramine and then injected with an agonist which was selective for one of the opiate receptor subtypes, µ1, µ2, a, k 1 or k 3. Analgesia was determined by a measurement of tail-flick latency when exposed to heat. These results were compared to control mice treated only with the selective agonists to facilitate the detection of in any potentiation of analgesic response and thus any involvement of the monoamines in analgesia. The results of these experiments demonstrated that serotonin was involved in the mediation of µ2 and k 1 analgesia. This was shown by significant shifts in the dose-response curves for the antinociceptive response when agonist injection was combined with pretreatment of zimelidine. Likewise, norepinephrine was found to be involved in the mediation of spinal a analgesia as shown by potentiation by desipramine. These findings help to clarify the mechanisms through which the different opioid receptors work to mediate analgesia.