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Differences in the structure of drinking, cart expression and dopamine turnover between polydipsic and non polydipsic rats in the quinpirole model of psychotic polydipsia

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Abstract

Rationale

Dopaminergic D2/D3 agonist quinpirole (QNP) elicits nonregulatory drinking in rats, a model of psychotic polydipsia. Why only a fraction of QNP-treated rats responds to the treatment becoming polydipsic is still unclear.

Objectives

To unveil possible factors contributing to such variability, we analyzed drinking microstructure in saline and QNP-treated rats, the hypothalamic expression of the cocaine and amphetamine regulated transcript (CART), and the monoaminergic turnover in selected brain areas.

Methods

Rats were daily treated with saline or QNP 0.5 mg/kg, and their 5-h water intake was measured for five consecutive days. The number of bouts and episodes of licking, and their duration, were also measured. Brain CART expression was measured by in situ hybridization and monoamines turnover by HPLC analysis of tissue extracts. Based on the amount of water ingested during the 5-h session, QNP-treated rats were post hoc grouped in polydipsic (PD) and in nonpolydipsic (NPD) rats, and the results compared accordingly.

Results

The number of drinking bouts and episodes increased in PD rats, while NPD rats behaved as the controls. CART expression decreased in the arcuate nucleus of the hypothalamus of the PD rats. In contrast, both PD and NPD rats showed a reduction of DA turnover in both ventral tegmental area (VTA) and nucleus accumbens (NAcc). No difference was detected in the turnover of 5HT and NA.

Conclusions

Microstructure analysis confirms that QNP acts on the appetitive component of drinking behavior, making it compulsive. CART expression reduction in response to dopaminergic hyperstimulation might sustain excessive drinking in PD rats.

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Acknowledgments

This study was financed by intramural grants from Sapienza University of Rome. The authors would like to thank Dr. Lorenza De Carolis for her technical support.

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Authors and Affiliations

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

    Chiara Schepisi, Silvia Cianci, Gaurav Bedse, Silvana Gaetani & Paolo Nencini

  2. Department of Pharmacology, Medical College, Xiamen University, Xiamen, Fujian, China

    Jin Fu

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  1. Chiara Schepisi
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  2. Silvia Cianci
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  3. Gaurav Bedse
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  4. Jin Fu
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  5. Silvana Gaetani
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  6. Paolo Nencini
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Correspondence to Paolo Nencini.

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Supplementary Table 1

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Fig. S1

Water intake calculated after excluding the two outliers from PD group (black circles = PD; gray triangles: NPD; white squares:VEH ). Data represents mean ± SEM. # and * p < .05 PD vs NPD and VEH, respectively. (JPEG 213 kb)

Fig. S2

Bars represent the mean ± SEM of bouts performed during each of the five hours of sessions (black bars for PD; gray bars for NPD; white bars for VEH) (JPEG 317 kb)

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Schepisi, C., Cianci, S., Bedse, G. et al. Differences in the structure of drinking, cart expression and dopamine turnover between polydipsic and non polydipsic rats in the quinpirole model of psychotic polydipsia. Psychopharmacology 231, 3889–3897 (2014). https://doi.org/10.1007/s00213-014-3527-0

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  • DOI: https://doi.org/10.1007/s00213-014-3527-0

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