Acute buspirone abolishes the expression of behavioral dopaminergic supersensitivity in mice

Abstract

Previous studies have shown that rats withdrawn from long-term treatment with dopamine receptor blockers exhibit dopaminergic supersensitivity, which can be behaviorally evaluated by enhanced general activity observed in an open-field. Recently, it has been reported that co-treatment with the non-benzodiazepine anxiolytic buspirone attenuates the development of haloperidol-induced dopaminergic supersensitivity measured by open-field behavior of rats. The aims of the present study were: 1) to determine, as previously reported for rats, if mice withdrawn from long-term neuroleptic treatment would also develop dopaminergic supersensitivity using open-field behavior as an experimental paradigm, and 2) to examine if acute buspirone administration would attenuate the expression of this behavioral dopaminergic supersensitivity. Withdrawal from longterm haloperidol treatment (2.5 mg/kg, once daily, for 20 days) induced a significant (30%) increase in ambulation frequency (i.e., number of squares crossed in 5-min observation sessions) but did not modify rearing frequency or immobility duration in 3-month-old EPM-M1 male mice observed in the open-field apparatus. Acute intraperitoneal injection of buspirone (3.0 and 10 but not 1.0 mg/kg, 12-13 animals per group) 30 min before open-field exposure abolished the increase in locomotion frequency induced by haloperidol withdrawal. These data suggest that the open-field behavior of mice can be used to detect dopaminergic supersensitivity, whose expression is abolished by acute buspirone administration.

Striatal 5-HT1A receptor stimulation reduces D1 receptor-induced dyskinesia and improves movement in the hemiparkinsonian rat

“…We recently found that systemic administration of the 5-HT 1A R agonist ±8-OH-DPAT reduced D1R agonist-induced dyskinesia while enhancing rotations, implicating an important functional role between 5-HT 1A R and D1R (Dupre et al, 2007). In line with these effects, 5-HT 1A R stimulation has been shown to reduce overactive striatal D1R-mediated signaling and D1R-mediated behaviors associated with the expression of LID (Queiroz et al, 2002; Tomiyama et al, 2005). …”

“…Although both receptor subtypes appear to be involved in LID, striatal D1R are particularly important (Cenci et al, 1998; Gerfen et al, 2002; Guigoni et al, 2007; Westin et al, 2007). For example, striatal preprodynorphin (PPD) mRNA associated with the D1R-expressing direct pathway (Anderson & Reiner, 1990) is increased in dyskinetic rats and primates and reduced by a number of anti-LID treatments (Cenci et al, 1998; Queiroz et al, 2002; Mela et al, 2007). Furthermore, coadministration of a D1R antagonist with L-DOPA has recently been shown to completely block the development of L-DOPA-induced dyskinesia and associated molecular abnormalities in a rodent model of LID (Westin et al, 2007).…”

Yokukansan Increases 5-HT1AReceptors in the Prefrontal Cortex and Enhances 5-HT1AReceptor Agonist-Induced Behavioral Responses in Socially Isolated Mice

“…The function of 5-HT 1A receptor in individual animals can be evaluated by differences in behavior after administration of a 5-HT 1A receptor agonist. Such responses include anxiolytic-like behavior in the open field and/or elevated plus maze [ 22 , 32 , 33 ], 5-HT syndrome (flat body posture, Straub tail response, hind limb abduction, forepaw treading, and head weaving behavior) [ 34 – 37 ], and hypothermic responses [ 38 , 39 ]. A dose-dependent decrease in rearing was observed following administration of buspirone, a 5-HT 1A receptor partial agonist, in the open field or elevated plus maze [ 32 , 33 ].…”

Effects of coincident 5-HT1A receptor stimulation and NMDA receptor antagonism on l-DOPA-induced dyskinesia and rotational behaviors in the hemi-parkinsonian rat

“…In fact, direct intrastriatal infusions of NMDAR antagonists produce both antiparkinsonian and anti-dyskinetic effects (Marin et al 1996;Nash et al 1999;Nash and Brotchie 2000). Similarly, stimulation of 5-HT 1A R within the motor cortex and/or striatum may convey anti-parkinsonian or anti-dyskinetic effects in part through a reduction of glutamate levels at the NMDAR (Antonelli et al 2005;Wolf 2005, 2007) via coincident effects on D1R-mediated signaling (Queiroz et al 2002;Tomiyama et al 2005;Ba et al 2006;Campbell et al 2006). Clearly, further work is necessary to investigate these novel results.…”