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Clomipramine, but not haloperidol or aripiprazole, inhibits quinpirole-induced water contrafreeloading, a putative animal model of compulsive behavior

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Abstract

Rationale

Repeated administrations of the D2/D3 agonist quinpirole (QNP) to rats elicit an antieconomical pattern of drinking called “contrafreeloading” (CFL), a putative model of compulsive-like behavior.

Objectives

We tested the sensitivity of QNP-induced CFL to haloperidol (HAL), aripiprazole (ARI), and clomipramine (CIM), the latter proven effective in the treatment of obsessive–compulsive disorder (OCD).

Methods

Rats were trained under a schedule of reinforcement (FR3) for water. On days 1–6, water was only available through lever pressing. On days 7–15, a choice between operant and free access was provided. QNP 0.5 mg/kg was administered alone or in combination with HAL (0.1 or 0.2 mg/kg), ARI (0.3 or 1 mg/kg), or CIM (5 or 10 mg/kg).

Results

Acutely QNP suppressed operant behavior and, therefore, water intake; upon repeated administrations, tolerance developed to this suppressant effect on responding but only to a lesser extent to the antidipsic effect. In choice conditions, QNP induced a progressive preference for the operant access (CFL). HAL per se, but not CIM and ARI, significantly reduced both responding and drinking (operant phase). In the choice phase, HAL and CIM inhibited CFL, but only the latter reinstated total water intake. ARI, in combination with QNP, increased responding.

Conclusions

CIM reinstates control patterns of drinking, while HAL and ARI where partially or not effective at all, respectively. As far as CIM is considered a first line treatment in OCD, these results further strengthen the notion that QNP-induced CFL belongs to the realm of dopaminergic drug-induced compulsive behaviors.

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Authors and Affiliations

  1. Department of Physiology and Pharmacology “Vittorio Erspamer”, Sapienza University of Rome, Italy, 5 Piazzale Aldo Moro, 00185, Rome, Italy

    Lorenza De Carolis, Chiara Schepisi, Michele S. Milella & Paolo Nencini

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  1. Lorenza De Carolis
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  2. Chiara Schepisi
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  3. Michele S. Milella
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  4. Paolo Nencini
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Corresponding author

Correspondence to Paolo Nencini.

Additional information

Lorenza De Carolis and Chiara Schepisi equally contributed to the study.

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Fig. S1

Effect of QNP 0.5 mg/kg alone or in combination with HAL 0.1 or 0.2 mg/kg (upper row), ARI 0.3 or 1 mg/kg (middle row) and CIM 5 or 10 mg/kg (lower row) on percentage of water consumed/water gained from the dipper through lever pressing in operant (left side) and in choice phase (right side). Data are expressed as mean±SEM of cumulative 6 and 9 days of treatment for operant and choice phase, respectively. Post-hoc Bonferroni test, *P < 0.05 vs. veh + veh and #P < 0.05 vs. veh + QNP (PDF 344 kb)

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De Carolis, L., Schepisi, C., Milella, M.S. et al. Clomipramine, but not haloperidol or aripiprazole, inhibits quinpirole-induced water contrafreeloading, a putative animal model of compulsive behavior. Psychopharmacology 218, 749–759 (2011). https://doi.org/10.1007/s00213-011-2372-7

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