Effects of the 5HT2C antagonist SB242084 on the pramipexole-induced potentiation of water contrafreeloading, a putative animal model of compulsive behavior

Abstract

CFL, but not polydipsia, was induced by preferential D3 activation, an effect prevented by 5HT2c receptor blockade. Since PPX interferes with decision making and 5HT2c receptor supersensitivity is involved in the expression of compulsive behaviors, this study supports the compulsive nature of dopaminergic-induced CFL.

Inhibition of hippocampal plasticity in rats performing contrafreeloading for water under repeated administrations of pramipexole

“…injected immediately before testing. The dose of 0.5 mg/kg for PPX was selected based on our previous work (Schepisi et al 2013). …”

“…In particular, we repeatedly found that when water-deprived rats are given the choice between responding for water (contingent access) and having it for free (noncontingent access), they exhibit CFL. Interestingly, CFL is sensitive to dopaminergic manipulations as both the dopaminergic D2-preferring agonist quinpirole (QNP) or the D3-preferring agonist pramipexole (PPX) strongly facilitate CFL by unbalancing the choice of animals toward the contingent access (Cioli et al 2000;Schepisi et al 2013). Nevertheless, while spontaneous CFL flexibly adapts to changing reinforcement contingencies (Osborne 1977), CFL induced by dopaminergic drugs is insensitive to manipulation of behavioral cost (Milella et al 2008) or reinforce palatability (Amato et al 2006).…”

“…Nevertheless, while spontaneous CFL flexibly adapts to changing reinforcement contingencies (Osborne 1977), CFL induced by dopaminergic drugs is insensitive to manipulation of behavioral cost (Milella et al 2008) or reinforce palatability (Amato et al 2006). Moreover, the finding that not all the water gained is actually consumed by QNP-or PPX-treated rats indicates that CFL is no longer focused on resource achievement (De Carolis et al 2011;Schepisi et al 2013). Taken together, these results suggest that CFL induced by dopaminergic drugs models some key hallmarks of the obsessive-compulsive disorder (OCD) in that the contingent response is excessive, time consuming, and disconnected to the outcome it is performed for.…”

“…The translational value of compulsive CFL was strengthened by findings showing that PPX, which potentiates CFL in rats (Schepisi et al 2013), induces compulsive behaviors in humans (Weintraub et al 2010;Moore et al 2014). Moreover, the finding that QNP-and PPX-induced CFL is suppressed by drugs that enhance the serotoninergic tone, such as clomipramine, or by the 5HT2c antagonist SB242084 (De Carolis et al 2011;Schepisi et al 2013) confers to CFL a solid OCD predictive validity (D'Angelo et al 2013;Alonso et al 2015).…”

“…Moreover, the finding that QNP-and PPX-induced CFL is suppressed by drugs that enhance the serotoninergic tone, such as clomipramine, or by the 5HT2c antagonist SB242084 (De Carolis et al 2011;Schepisi et al 2013) confers to CFL a solid OCD predictive validity (D'Angelo et al 2013;Alonso et al 2015).…”