Differences in the Structure of Drinking, Cart Expression and Dopamine Turnover Between Polydipsic and Non Polydipsic Rats in the Quinpirole Model of Psychotic Polydipsia

Overview

Journal Psychopharmacology (Berl)

Specialty Pharmacology

Date 2014 Mar 21

PMID 24647922

Citations 4

Authors

Chiara Schepisi

Silvia Cianci

Gaurav Bedse

Jin Fu

Silvana Gaetani

Paolo Nencini

Affiliations

Soon will be listed here.

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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References

Schepisi C, De Carolis L, Nencini P . Effects of the 5HT2C antagonist SB242084 on the pramipexole-induced potentiation of water contrafreeloading, a putative animal model of compulsive behavior. Psychopharmacology (Berl). 2012; 227(1):55-66. DOI: 10.1007/s00213-012-2938-z. View

Badiani A, Vaccaro R, Burdino R, Casini A, Valeri P, Renda T . Dissociation in the effects of the D2/D3 dopaminergic agonist quinpirole on drinking and on vasopressin levels in the rat. Neurosci Lett. 2002; 325(2):79-82. DOI: 10.1016/s0304-3940(02)00261-6. View

Fraioli S, Cioli I, Nencini P . Amphetamine reinstates polydipsia induced by chronic exposure to quinpirole, a dopaminergic D2 agonist, in rats. Behav Brain Res. 1998; 89(1-2):199-215. DOI: 10.1016/s0166-4328(97)00063-6. View

Job M, Licata J, Hubert G, Kuhar M . Intra-accumbal administration of shRNAs against CART peptides cause increases in body weight and cocaine-induced locomotor activity in rats. Brain Res. 2012; 1482:47-54. PMC: 3487597. DOI: 10.1016/j.brainres.2012.09.005. View

Liang S, Pan J . Pretreatment with antisense oligodeoxynucleotide against D(2) or D(3) receptor mRNA diminished dopamine's inhibitory effect on dorsomedial arcuate neurons in brain slices of estrogen-treated ovariectomized rats. Brain Res. 2002; 926(1-2):156-64. DOI: 10.1016/s0006-8993(01)03314-5. View

Castaneda E, Becker J, Robinson T . The long-term effects of repeated amphetamine treatment in vivo on amphetamine, KCl and electrical stimulation evoked striatal dopamine release in vitro. Life Sci. 1988; 42(24):2447-56. DOI: 10.1016/0024-3205(88)90343-8. View

Kim S, Yoon H, Kim J . CART peptide 55-102 microinjected into the nucleus accumbens inhibits the expression of behavioral sensitization by amphetamine. Regul Pept. 2007; 144(1-3):6-9. DOI: 10.1016/j.regpep.2007.07.003. View

Nakhate K, Kokare D, Singru P, Taksande A, Kotwal S, Subhedar N . Hypothalamic cocaine- and amphetamine-regulated transcript peptide is reduced and fails to modulate feeding behavior in rats with chemically-induced mammary carcinogenesis. Pharmacol Biochem Behav. 2010; 97(2):340-9. DOI: 10.1016/j.pbb.2010.09.001. View

Tessner K, Walker E, Dhruv S, Hochman K, Hamann S . The relation of cortisol levels with hippocampus volumes under baseline and challenge conditions. Brain Res. 2007; 1179:70-8. DOI: 10.1016/j.brainres.2007.05.027. View

10.

Dvorkin A, Culver K, Szechtman H . Differential effects of clorgyline on sensitization to quinpirole in rats tested in small and large environments. Psychopharmacology (Berl). 2006; 186(4):534-43. DOI: 10.1007/s00213-006-0377-4. View

11.

Higgs S, Cooper S . The effect of the dopamine D2 receptor antagonist raclopride on the pattern of licking microstructure induced by midazolam in the rat. Eur J Pharmacol. 2000; 409(1):73-80. DOI: 10.1016/s0014-2999(00)00802-5. View

12.

Flagel S, Robinson T, Clark J, Clinton S, Watson S, Seeman P . An animal model of genetic vulnerability to behavioral disinhibition and responsiveness to reward-related cues: implications for addiction. Neuropsychopharmacology. 2009; 35(2):388-400. PMC: 2794950. DOI: 10.1038/npp.2009.142. View

13.

Robinson T, Becker J . Enduring changes in brain and behavior produced by chronic amphetamine administration: a review and evaluation of animal models of amphetamine psychosis. Brain Res. 1986; 396(2):157-98. DOI: 10.1016/s0006-8993(86)80193-7. View

14.

Schneider L, Davis J, Watson C, Smith G . Similar effect of raclopride and reduced sucrose concentration on the microstructure of sucrose sham feeding. Eur J Pharmacol. 1990; 186(1):61-70. DOI: 10.1016/0014-2999(90)94060-b. View

15.

Kristensen P, JUDGE M, Thim L, Ribel U, Christjansen K, Wulff B . Hypothalamic CART is a new anorectic peptide regulated by leptin. Nature. 1998; 393(6680):72-6. DOI: 10.1038/29993. View

16.

Szumlinski K, Goodwill A, Szechtman H . Locomotor sensitization to quinpirole in rats: effects of drug abstinence and sex. Psychopharmacology (Berl). 2000; 152(3):304-11. DOI: 10.1007/s002130000538. View

17.

De Carolis L, Stasi M, Serlupi-Crescenzi O, Borsini F, Nencini P . The effects of clozapine on quinpirole-induced non-regulatory drinking and prepulse inhibition disruption in rats. Psychopharmacology (Berl). 2010; 212(1):105-15. DOI: 10.1007/s00213-010-1937-1. View

18.

Goldman M, Gomes A, Carter C, Lee R . Divergent effects of two different doses of intranasal oxytocin on facial affect discrimination in schizophrenic patients with and without polydipsia. Psychopharmacology (Berl). 2011; 216(1):101-10. DOI: 10.1007/s00213-011-2193-8. View

19.

Jaworski J, Hansen S, Kuhar M, Mark G . Injection of CART (cocaine- and amphetamine-regulated transcript) peptide into the nucleus accumbens reduces cocaine self-administration in rats. Behav Brain Res. 2008; 191(2):266-71. PMC: 2497435. DOI: 10.1016/j.bbr.2008.03.039. View

20.

Rowland N, Antelman S, Kocan D . Elevated water intake in rats treated chronically with amphetamine: drinking in excess of need?. Appetite. 1981; 2(1):51-66. DOI: 10.1016/s0195-6663(81)80036-0. View