Stimulus properties of fluvoxamine in a conditioned taste aversion procedure

Abstract

A conditioned taste aversion (CTA) procedure in mice was used to investigate the stimulus effects of the serotonin reuptake inhibitors (SSRIs) fluvoxamine and fluoxetine. Fluvoxamine elicited a reliable CTA (ED50 = 24 mg/kg, SC) and a number of drugs were tested as pre-exposure drugs. Pre-exposure to the serotonin (5-HT)1A receptor agonists flesinoxan and +/- -8-hydroxy-dipropylaminotetralin (8-OH-DPAT) prevented the CTA induced by fluvoxamine (50 mg/kg, SC). Pre-exposure with the 5-HT2C receptor agonist MK 212 [6-chloro-2(1-piperazinyl)pyrazine] partially prevented the fluvoxamine-induced CTA, pre-exposure with the 5-HT2A/2C receptor agonist DOI [1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl] did not prevent the CTA induced by fluvoxamine. Flesinoxan pre-exposure also prevented the taste aversion induced by fluoxetine (10 mg/kg, SC) completely. This contrasts previous results obtained with fluoxetine, where was found that its stimulus is primarily mediated by 5-HT2C, and to a lesser degree by 5-HT1A receptors. Therefore, we compared the two SSRIs directly. Pre-exposure to fluvoxamine prevented the fluoxetine-induced CTA, whereas pre-exposure to fluoxetine only partially prevented the fluvoxamine-induced CTA. We conclude that 5-HT1A receptors are involved in the stimulus properties of both fluvoxamine and fluoxetine, that 5-HT2C receptors are involved in fluvoxamine and especially fluoxetine, and, based primarily on the cross-comparison tests, that the two SSRIs have somewhat different stimulus properties.

The selective serotonin re-uptake inhibitors fluvoxamine and paroxetine differ in sexual inhibitory effects after chronic treatment

“…A possible alternative explanation is that these SSRIs may have differential effects on 5-HT receptors. An indication for an indirect stimulating effect of fluvoxamine on 5-HT 1A receptors is found in a crossfamiliarization conditioned taste aversion (CTA)-procedure in mice (Gommans et al 1998). Although only fluvoxamine and fluoxetine were investigated, clear differences between these two SSRIs emerged, indicating that fluvoxamine may exert its effects primarily via 5-HT 1A receptors and fluoxetine primarily via 5-HT 2C receptors.…”

“…Prior to the present and previous experiments (Mos et al 1999), we did extensive dose-ranging studies to detect the optimal dose of each SSRI that did not lead to sedation, thus ruling out the latter as a possible explanation of the distinctive behavioral effects. Moreover, the actual doses of paroxetine and fluvoxamine used correspond with effective doses of these SSRIs in other experimental paradigms (Olivier et al 1993Gommans et al 1998).…”

In vivo modulation of vagal‐identified dorsal medullary neurones by activation of different 5‐Hydroxytryptamine2 receptors in rats

“…The e ects of this ligand appeared within the ®rst 5 s of application, and returned to control after the application. In some cells, DOI (20 ± 50 nA, 23/58) and/or MK-212 (10 ± 50 nA, 20/58), a selective 5-HT 2C receptor agonist (Gommans et al, 1998;Halford et al, 1997), were applied in addition to BW-723C86 (in order to identify the receptor(s) involved in the 5-HT 2 receptor activation) ( Table 1).…”

The stimulus properties of LSD in C57BL/6 mice

“…Nonetheless, the stimulus properties of a number of drugs have been examined in mice as well. These represent a range of pharmacological classes including stimulants such as cocaine [Middaugh et al, 1998] the amphetamines [Snoddy and Tessel;1983], nicotine [Varvel et al, 1999;Stolerman et al 1999], and pentylenetetrazole [Evans and Balster, 1992], the depressants morphine [Borlongan and Watanabe, 1997], pentobarbital [Balster and Moser, 1987;Rees and Balster, 1988], oxazepam [Rees and Balster, 1988], and ethanol [Rees and Balster, 1988;Grant et al, 1991;Middaugh et al, 1991], non-competitive NMDA antagonists including phencyclidine [Middaugh et al, 1988;English et al, 1999] and dizocilpine [Geter-Douglas and Witkin, 1999] as well as monoamine reuptake inhibitors [fluvoxamine, Gommans et al, 1998;nisoxetine, Snoddy and Tessel;1983] and the atypical antipsychotic agent, clozapine [Philibin et al, 2005]. In the first, and at this time only, report of stimulus control by a hallucinogen in mice, Smith, Barrett, and Sanders-Bush [2003] employed the phenethylamine hallucinogen, 2,5-dimethoxy-4-iodo-amphetamine [DOI; Shulgin and Shulgin, 1991].…”