Central overexpression of angiotensin AT(1A) receptors prevents dopamine D(2) receptor regulation of alcohol consumption in mice.

BACKGROUND While angiotensin receptors are found on the soma and terminals of dopaminergic neurons, controversy surrounds the potential role of angiotensin in alcohol consumption. METHODS Using a transgenic mouse with a brain-specific overexpression of angiotensin AT(1A) receptors (NSE-AT(1A) mice), we have examined the role of angiotensin in alcohol consumption and alcohol-induced regulation of the dopaminergic system. RESULTS The functional relevance of the overexpressed AT(1A) receptors was confirmed by an exaggerated rehydration response following 24-hour dehydration. NSE-AT(1A) mice showed a high preference for alcohol (similar to wild-type mice); yet, raclopride treatment had no effect on alcohol consumption in NSE-AT(1A) mice, while significantly reducing consumption in wild-type mice. In contrast, NSE-AT(1A) mice showed enhanced sensitivity to raclopride compared with wild types in terms of D(2) receptor up-regulation within the ventral mesencephalon. In addition, striatal D(2) receptors in NSE-AT(1A) mice were sensitive to up-regulation by chronic alcohol consumption. CONCLUSIONS Collectively, these data imply that while expression of angiotensin AT(1A) receptors on striatal neurons has no impact upon basal alcohol consumption or preference, AT(1A) receptors do modulate the sensitivity of dopamine D(2) receptors to regulation by alcohol and the ability of a D(2) receptor antagonist to reduce consumption.

[1]  T. Walther,et al.  Lack of angiotensin II conversion to angiotensin III increases water but not alcohol consumption in aminopeptidase A-deficient mice , 2006, Regulatory Peptides.

[2]  M. Low,et al.  Reduced basal and ethanol stimulation of striatal extracellular dopamine concentrations in dopamine D2 receptor knockout mice , 2006, Synapse.

[3]  A. Lawrence,et al.  Alcoholism and neuropeptides: an update. , 2006, CNS & neurological disorders drug targets.

[4]  C. Ledent,et al.  Receptor Crosstalk: Characterization of Mice Deficient in Dopamine D1 and Adenosine A2A Receptors , 2006, Neuropsychopharmacology.

[5]  A. Lawrence,et al.  The Metabotropic Glutamate 5 Receptor Antagonist 3-[(2-Methyl-1,3-thiazol-4-yl)ethynyl]-pyridine Reduces Ethanol Self-Administration in Multiple Strains of Alcohol-Preferring Rats and Regulates Olfactory Glutamatergic Systems , 2005, Journal of Pharmacology and Experimental Therapeutics.

[6]  T. Walther,et al.  Central angiotensin II controls alcohol consumption via its AT1 receptor , 2005, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[7]  N. Volkow,et al.  Dopamine D2R DNA transfer in dopamine D2 receptor-deficient mice: effects on ethanol drinking. , 2005, Life sciences.

[8]  A. Lawrence,et al.  Renovascular Hypertension in Mice With Brain-Selective Overexpression of AT1a Receptors Is Buffered by Increased Nitric Oxide Production in the Periphery , 2004, Circulation research.

[9]  É. Fekete,et al.  Angiotensin II and III microinjections into the zona incerta influence drinking behavior , 2003, Brain Research.

[10]  A. Johnson,et al.  Investigations on the physiological controls of water and saline intake in C57BL/6 mice. , 2003, American journal of physiology. Regulatory, integrative and comparative physiology.

[11]  I. McGregor,et al.  Increased Anxiety 3 Months after Brief Exposure to MDMA (‘Ecstasy’) in Rats: Association with Altered 5-HT Transporter and Receptor Density , 2003, Neuropsychopharmacology.

[12]  A. Lawrence,et al.  The Effect of Chronic Ethanol Consumption and Withdrawal on μ-Opioid and Dopamine D1 and D2 Receptor Density in Fawn-Hooded Rat Brain , 2002, Journal of Pharmacology and Experimental Therapeutics.

[13]  S. Dunlay,et al.  Brain-Selective Overexpression of Angiotensin (AT1) Receptors Causes Enhanced Cardiovascular Sensitivity in Transgenic Mice , 2002, Circulation research.

[14]  A. Lawrence,et al.  Alterations in central preproenkephalin mRNA expression after chronic free-choice ethanol consumption by fawn-hooded rats. , 2001, Alcoholism, clinical and experimental research.

[15]  M. Bader,et al.  Alcohol consumption is controlled by angiotensin II , 2001, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[16]  Yanfang Chen,et al.  Differentiation of Brain Angiotensin Type 1a and 1b Receptor mRNAs: A Specific Effect of Dehydration , 2001, Hypertension.

[17]  J. Blair‐West,et al.  Angiotensin II Stimulates Intake of Ethanol in C57BL/6J Mice , 1999, Physiology & Behavior.

[18]  J. Blair‐West,et al.  Intracerebroventricular infusion of angiotensin II increases water and ethanol intake in rats. , 1999, American journal of physiology. Regulatory, integrative and comparative physiology.

[19]  T. Coffman,et al.  Neuroendocrine effects of dehydration in mice lacking the angiotensin AT1a receptor. , 1999, Hypertension.

[20]  George Paxinos,et al.  The Mouse Brain in Stereotaxic Coordinates , 2001 .

[21]  C. Hodge,et al.  Alcohol self-administration: further examination of the role of dopamine receptors in the nucleus accumbens. , 1997, Alcoholism, clinical and experimental research.

[22]  J. Blair‐West,et al.  The dipsogen angiotensin II does not stimulate ethanol intake in mice , 1996, Physiology & Behavior.

[23]  B. Carr,et al.  Angiotensin II reduces alcohol intake and choice in water- or food-restricted rats. , 1996, Alcohol.

[24]  Christer Halldin,et al.  Autoradiographic localization of extrastriatal D2‐dopamine receptors in the human brain using [125I]epidepride , 1996, Synapse.

[25]  G. Beauchamp,et al.  Ethanol consumption and taste preferences in C57BL/6ByJ and 129/J mice. , 1996, Alcoholism, clinical and experimental research.

[26]  M. Druse,et al.  Effects of chronic alcohol consumption and aging on dopamine D1 receptors in Fischer 344 rats. , 1995, Alcoholism, clinical and experimental research.

[27]  L. Grupp,et al.  Intracerebroventricularly infused angiotensin II or III do not alter voluntary alcohol intake in rats , 1995, Pharmacology Biochemistry and Behavior.

[28]  A. Lawrence,et al.  Functional dopamine D2 receptors on rat vagal afferent neurones , 1995, British journal of pharmacology.

[29]  Christer Halldin,et al.  Distribution of D1- and D2-Dopamine Receptors, and Dopamine and Its Metabolites in the Human Brain , 1994, Neuropsychopharmacology.

[30]  L. Grupp,et al.  The reduction in alcohol drinking by peripherally injected angiotensin II is selectively mediated by the AT1 receptor subtype , 1994, Pharmacology Biochemistry and Behavior.

[31]  C. Hodge,et al.  Effect of dopamine agonists and antagonists on ethanol-reinforced behavior: The involvement of the nucleus accumbens , 1993, Brain Research Bulletin.

[32]  Ting-kai Li,et al.  Effects of D1 and D2 dopamine receptor agents on ethanol consumption in the high-alcohol-drinking (HAD) line of rats. , 1993, Alcohol.

[33]  D. A. Fitts.  Angiotensin and captopril increase alcohol intake , 1993, Pharmacology Biochemistry and Behavior.

[34]  G. Donnan,et al.  Angiotensin II receptor binding associated with nigrostriatal dopaminergic neurons in human basal ganglia , 1992, Annals of neurology.

[35]  L. Grupp.  Effects of angiotensin II and an angiotensin converting enzyme inhibitor on alcohol intake in P and NP rats , 1992, Pharmacology Biochemistry and Behavior.

[36]  G. Paxinos,et al.  Localization and characterization of angiotensin II receptor binding sites in the human basal ganglia, thalamus, midbrain pons, and cerebellum , 1991, The Journal of comparative neurology.

[37]  W. Mcbride,et al.  Microinjection of sulpiride into the nucleus accumbens increases ethanol drinking in alcohol-preferring (P) rats. , 1991, Alcohol and alcoholism (Oxford, Oxfordshire). Supplement.

[38]  L. Grupp,et al.  Angiotensin converting enzyme inhibitors reduce alcohol consumption: some possible mechanisms and important conditions for its therapeutic use. , 1990, Alcoholism, clinical and experimental research.

[39]  R. Stewart,et al.  Systemic angiotensin II acts at the subfornical organ to suppress voluntary alcohol consumption , 1989, Pharmacology Biochemistry and Behavior.

[40]  F. Leenen,et al.  Alcohol intake is inversely related to plasma renin activity in the genetically selected alcohol-preferring and -nonpreferring lines of rats , 1989, Pharmacology Biochemistry and Behavior.

[41]  R. Stewart,et al.  Angiotensin II-induced suppression of alcohol intake and its reversal by the angiotensin antagonist Sar-1 Thr-8 angiotensin II , 1988, Pharmacology Biochemistry and Behavior.

[42]  R. Stewart,et al.  Angiotensin converting enzyme inhibitors: animal experiments suggest a new pharmacological treatment for alcohol abuse in humans. , 1988, Alcoholism, clinical and experimental research.

[43]  H. Samson,et al.  Haloperidol and apomorphine effects on ethanol reinforcement in free feeding rats , 1988, Pharmacology Biochemistry and Behavior.

[44]  R. Abhold,et al.  Elevations in plasma angiotensin II with prolonged ethanol treatment in rats , 1986, Pharmacology Biochemistry and Behavior.

[45]  R. Vandongen,et al.  Alcohol stimulation of renin release in man: its relation to the hemodynamic, electrolyte, and sympatho-adrenal responses to drinking. , 1985, The Journal of clinical endocrinology and metabolism.