Effects of housing, restraint and chronic treatments withmCPP and sertraline on behavioural responses tomCPP

Abstract

The effects of pretreatments on behavioural responses to activation of 5-HT1C receptors by m-chlorophenylpiperazine (mCPP) were investigated. The hypo locomotor and anxiogenic effects of mCPP (social interaction test) were influenced neither by previous housing (single versus grouped) nor by restraint (2 h, 24 h previously). In the absence of mCPP, 24 h group housing led to decreased social interaction and the restraint procedure led to significant decreases of feeding and locomotion. The hypophagic effect of mCPP was unaffected by previous restraint. However, chronic pretreatment with mCPP (2.5 mg/kg per day IP x 14) or with the antidepressant 5-HT reuptake inhibitor sertraline (5 mg/kg per day SC x 14) attenuated all three behaviours. The above findings are discussed with respect to published data on effects of pretreatments on responses to the activation of 5-HT1C receptors.

Oral administration of the 5-HT2C receptor agonist, mCPP, reduces body weight gain in rats over 28 days as a result of maintained hypophagia

“…This is most marked with d-fenfluramine, though also evident with mCPP. This apparent partial tolerance has been observed previously for both compounds (Sills et al 1985;Freo et al 1992;Kennedy 1993;Vickers et al 2000).…”

Ethopharmacological analysis of the unstable elevated exposed plus maze, a novel model of extreme anxiety: predictive validity and sensitivity to anxiogenic agents

“…Furthermore, increases in anxiety despite overall locomotor suppression are also documented (e.g. social interaction test: Kennedy et al 1993;elevated plus-maze: Fone et al 1996; canopy stretched attend posture test: Grewal et al 1997). Correspondingly, Meert et al (1997) have found that mCPP treated animals appear to be generally aroused, as evidenced by a doserelated increase in plasma prolactin and ACTH levels, in spite of a decrement in locomotor performance.…”

Differential effects of acute and chronic fluoxetine administration on the spontaneous activity of dopaminergic neurones in the ventral tegmental area

“…Moreover, chronic treatments with citalopram and sertaline, two potent SSRIs, were found to attenuate the hypolocomotor effect of mCPP (Maj & Moryl, 1992;Kennedy et al, 1993). Since it is thought that mCPP reduces locomotor activity in rodents by stimulating the 5-HT2C/2B receptors (Kennett & Curzon, 1988;Kennett et al, 1994b), it has been argued that a down-regulation of 5-HT2c,2B recpetors might be responsible for the behavioural tolerance to mCPP occurring after chronic administration of SSRIs (Kennedy et al, 1993;Kennett et al, 1994a). This is reconcilable with the evidence that mCPP inhibits the activity of dopaminergic neurones in the VTA by acting through the 5-HT2C/2B receptors (Prisco et al, 1994).…”