Effect of chronic and acute administration of fluoxetine and its additive effect with morphine on the behavioural response in the formalin test in rats

Abstract

Serotonergic systems are involved in the central regulation of nociceptive sensitivity. Fluoxetine, a selective inhibitor of the reuptake of serotonin (5-hydroxytryptamine, 5-HT), was administered orally (0.16, 0.32, 0.8 mg kg(-1) daily for 7 days), intraperitoneally (0.04, 0.08, 0.16 mg kg(-1) day(-1) for 7 days and a single dose of 0.32 mg kg(-1)) and intracerebroventricularly (10 microg/rat) to rats and nociceptive sensitivity was evaluated using the formalin test (50 microL of 2.5% formalin injected subcutaneously). The effect of fluoxetine was also studied in the presence of 5,7-dihydroxytryptamine creatinine sulfate (5,7-DHT) and after co-administration with morphine. Oral (0.8 mg kg(-1)), intraperitoneal (0.16 and 0.32 mg kg(-1)) and intracerebroventricular (10 microg/rat) fluoxetine induced antinociception in the late phase of the formalin test. Furthermore, intrathecal administration of 5-HT (100 microg/rat) induced an analgesic effect. The analgesic effect of fluoxetine (0.16 and 0.32 mg kg(-1), i.p.) and 5-HT (100 microg/rat, i.t.) was abolished by pre-treatment with 5,7-DHT (100 microg/rat, i.t.). In addition, the analgesic effect of 5-HT (100 microg/rat, i.t.) was decreased by pre-treatment with naloxone (2 mg kg(-1), i.p.). Morphine (5 mg kg(-1), i.p.) induced analgesia that was increased by fluoxetine (0.32 mg kg(-1), i.p.). These results suggest that fluoxetine has an antinociceptive effect in tonic inflammatory pain through functional alteration of the serotonergic system and also potentiates the analgesic effect of morphine.

Antinociceptive Interactions between Mu-Opioid Receptor Agonists and the Serotonin Uptake Inhibitor Clomipramine in Rhesus Monkeys: Role of Mu Agonist Efficacy

“…Thus, clomipramine interactions with analgesia-related effects of nalbuphine were similar in both procedures. These results agree with the finding that the serotonin uptake inhibitor fluoxetine enhanced effects of morphine in the formalin test in rats (Nayebi et al, 2001).…”

Modification of Fentanyl Analgesia by Antidepressants

“…1 ). An increase in analgesic action of morphine after a single dose of fluoxetine was reported by Nayebi et al [8] and Erjavec et al [9] , which was not confirmed in the present study.…”

“…In fact, a single dose of fluoxetine resulted in analgesia [8] and increased the analgesic action of morphine [9] . However, the mechanism or mechanisms of this interaction are still unclear.…”

Long-term effects of fluoxetine or vehicle administration during pregnancy on behavioral outcomes in guinea pig offspring

“…5-HT is known to be involved in the regulation of nociception at both spinal and supraspinal levels (Messing and Lytle 1977), with enhanced serotonergic transmission resulting in analgesia. Fluoxetine has been shown to have analgesic activity in several pain models, including thermal pain, when administered to rats, mice, or monkeys (Gatch et al 1998;Nayebi et al 2001;Singh et al 2001) as well as in the clinical treatment of pain in humans (Ansari 2000). However, this is the first study to provide evidence that administration of fluoxetine to the pregnant animal can have lasting antinociceptive effects in the offspring.…”