Selective agonists and antagonists for 5-hydroxytryptamine receptor subtypes, and interactions with yohimbine and FG 7142 using the elevated plus-maze test in the rat

Abstract

The effects of some 5-HT receptor ligands were investigated on measures of anxiety in an elevated plus-maze test in the rat. Quipazine (2 and 4 mg kg-1), a non-specific 5-HT agonist and ritanserin (0.25-10 mg kg-1), a 5-HT2 receptor antagonist displayed anxiogenic profiles by reducing both of the measures of anxiety used in this test. Two 5-HT1A receptor ligands, buspirone (4 and 8 mg kg-1) and ipsapirone (2.5-10 mg kg-1) and the 5-HT1 agonist, RU 24969 (0.1875-1.5 mg kg-1) significantly reduced only the percentage of time spent on the open arms. (-)-Propranolol (5 and 10 mg kg-1), a 5-HT1 receptor antagonist significantly reduced only the percentage of entries made onto the open arms. Metergoline (4 mg kg-1), a non-specific 5-HT antagonist displayed anxiolytic effects in this test by increasing both measures of anxiety. The 5-HT1A receptor agonist, 8-OH-DPAT (0.0625-0.25 mg kg-1) had no effect on either of the measures of anxiety. The results from the non-specific ligands (quipazine and metergoline) are consistent with the theory that a reduction in 5-HT function reduces anxiety. However, in spite of their more selective effects on 5-HT receptors the results in this test from the more specific ligands are not consistent with a strong involvement of any single receptor subtype. The interaction studies with yohimbine and FG 7142 (beta-carboline-3-carboxylate methylamide) provided no clear evidence for a major role of 5-HT pathways in the mediation of their anxiogenic effects.

The profiles of interaction of yohimbine with anxiolytic and putative anxiolytic agents to modify 5‐HT release in the frontal cortex of freely‐moving rats

“…Using the in vivo microdialysis technique, the present study has demonstrated that the systemic administration of the M2-adrenoceptor antagonist, yohimbine, having anxiogenic properties in animal models of anxiety and man (Charney et al, 1983;1992;Pellow et al, 1987), significantly increased the extracellular levels of 5-HT in the frontal cortex of the freely-moving rat. Yohimbine also caused a slight but significant reduction in the frontal cortical dialysate 5-HIAA levels.…”

Locomotor response to MDMA is attenuated in knockout mice lacking the 5-HT 1B receptor

“…However, in previous studies with rats, the center-avoiding behavior induced by MDMA was not interpreted as evidence of increased anxiety, because familiarization with the testing environment fails to change the pattern of locomotor activity (Callaway et al 1991). On the other hand, 5-HT 1B agonists have been shown to increase anxiety in rodents (Pellow et al 1987). Without testing the effect of MDMA on a more direct measure of anxiety, such as ultrasonic vocalization in pups or elevated plus-maze behavior, it is difficult to tell whether the center-avoiding behavior seen in WT, but not KO, mice reflects the 5-HT 1B receptor's role in anxiety or its characteristic influence on the pattern of locomotor activation.…”

Functional Neuropharmacology of Compounds Acting at 5-HT1B/D Receptors

“…Various agonists that exhibit a certain selectivity for 5-HT 1ll receptors, such as RU 24969, TFMPP and eltoprazine, show anxiogenic-like activity in animal models such as the shock probe conflict procedure (MEER! and COLPAERT 1986), the social interaction test and the elevated plus-maze test both in rats (PELLOW et al 1987) and in mice (BENJAMIN et al 1990;RODGERS et aL 1992), although results in conflict tests in rodents are more variable (DEACON and GARDNER 1986).…”