Effect of Serotonin 5-HT₁, 5-HT₂, and 5-HT₃ Receptor Antagonists on the Prolactin Response to Restraint and Ether Stress

Abstract

Serotonin (5-HT) appears to be involved in the central control of the prolactin (PRL) response to suckling and estrogen. Furthermore, 5-HT may participate in the mediation of stress-induced PRL release. In order further to elucidate the role of 5-HT and the type of 5-HT receptor(s) involved in the PRL response to stress, we investigated the effect of blockade of 5-HT₁, 5-HT₂ or 5-HT₃ receptors on the restraint or ether stress-induced release of PRL in male rats. Pretreatment with the 5-HT_{1 + 2} receptor antagonist methysergide (0.5 or 2.5 mg/kg i.p.) inhibited or prevented the PRL response to restraint or ether stress. Pretreatment with the 5-HT₂ receptor antagonists ketanserin or LY 53857 (0.5 or 2.5 mg/kg i.p.) inhibited the response to restraint or ether stress approximately 30 or 60%, respectively. Higher doses of both 5-HT₂ receptor antagonists (10 mg/kg i.p.) had a minor inhibitory effect (5-30% for ketanserin and 50% for LY 53857). Prior intraperitoneal administration of the 5-HT₃ receptor antagonists ICS 205-930 or GR 38032F (0.05-2.5 mg/kg i.p.) inhibited the restraint stress-induced PRL release dose-dependently. Both compounds inhibited the PRL response to ether stress, but only the effect of GR was dose-related. The maximal inhibitory effect (70% inhibition of the PRL response to restraint or ether stress) was obtained for both compounds at a dose of 0.1 mg/kg. We conclude that serotonergic neurons are involved in the mediation of the stress-induced PRL release by activation of 5-HT₁, 5-HT₂ as well as 5-HT₃ receptors.

Genetic variation in cortico-amygdala serotonin function and risk for stress-related disease

“…5-HT3A-R knockout mice show an attenuated adrenocorticotropin-releasing hormone response to restraint stress (Bhatnagar et al, 2004b;Bhatnagar and Vining, 2004) similar to the attenuated restraint stress-induced prolactin response produced by the 5-HT3-R antagonist ondansetron in rats (Jorgensen et al, 1992;Nonaka, 1999) (but see Jorgensen et al, 1998). By extension the elevated levels of CRH mRNA in the central nucleus of the amygdala of 5-HT3A-R knockout mice may be an upstream compensation for a chronically depressed HPA-axis (Bhatnagar et al, 2004b), although it could also reflect a loss of normal GABAergic facilitation mediated by this receptor in the amygdala Turner et al, 2004).…”

Serotonergic involvement in stress-induced vasopressin and oxytocin secretion

“…The antagonists (67) were infused intracerebroventricularly at 215 min, unless otherwise stated. The time for administration and the doses of antagonists were chosen on the basis of previous experiments, with the antagonists administered both intraperitoneally and intracerebroventricularly (30,32,33).…”

Interactions between N-methyl-D-aspartate, nitric oxide and serotonin in the control of prolactin secretion in prepubertal male rats

“…Activation of 5-HT 1 , 5-HT 2 and 5-HT 3 receptors increased PRL release (27)(28)(29)(30)(31). In our experiments, we have tested the possible role of NO in mediating the effects of 5-HTP, 8-OH-DPAT and DOI.…”