fg-9041 and Hypotension

Glutamatergic mechanisms have been implicated in the control of fluid ingestion. In the present study, we investigated whether non-N-methyl-d-aspartate (NMDA) glutamatergic receptors in the lateral parabrachial nucleus (LPBN) are involved in the control of water and sodium intake. Male Sprague-Dawley rats had cannulas implanted bilaterally into the LPBN. They were acutely depleted of water and sodium by injections of the diuretic furosemide (Furo; 10 mg/kg, bw) and given a low dose of the angiotensin-converting enzyme inhibitor, captopril (Cap; 5 mg/kg, bw). Bilateral LPBN injections of the non-NMDA receptor antagonist DNQX (2 and 5 nmol/0.2 microl) increased the ingestion of 0.3 M NaCl and water of Furo/Cap treated rats. The increased ingestion produced by DNQX was abolished by pretreating the LPBN with alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), a non-NMDA receptor agonist. AMPA injected alone into the LPBN reduced water and 0.3 M NaCl intake. Injections of DNQX (5 nmol/0.2 microl) into the LPBN also produced ingestion of 0.3 M NaCl after sc injections of the beta-adrenoceptor agonist, isoproterenol, a hypotensive drug that typically produces only water intake. Food intake, arterial blood pressure and heart rate were not altered by DNQX LPBN injections. We conclude that agonists acting on non-NMDA receptors in the LPBN exert an inhibitory influence on sodium intake during acute fluid depletion with hypotension and after isoproterenol treatment. A possible interaction of serotonin with glutamate within the LPBN is discussed.

Topics: alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; Analysis of Variance; Animals; Antihypertensive Agents; Appetite; Captopril; Catheters, Indwelling; Diuretics; Drinking; Eating; Excitatory Amino Acid Agonists; Excitatory Amino Acid Antagonists; Furosemide; Hypotension; Male; Pons; Quinoxalines; Rats; Rats, Sprague-Dawley; Receptors, AMPA; Sodium, Dietary; Time Factors; Water Deprivation

In a previous study it was shown that nitroprusside-induced hypotension strongly enhances the release of dopamine (DA) in the prefrontal cortex (PFC). In the present study we have further investigated the mechanism involved in this effect. Glutamate receptor antagonists were infused into the ventral tegmental area (VTA) or PFC, while DA release was measured in the ipsilateral PFC and hypotension was applied by intravenous infusion of nitroprusside. Infusion into the VTA of neither a NMDA receptor antagonist (CPP), nor a non-NMDA antagonist (DNQX) affected the hypotension-induced increase of DA in the PFC. Intracortical infusion of CPP also failed to affect significantly, whereas local infusion of DNQX inhibited the hypotension-enhanced release of DA dose-dependently. The stimulation of DA release was relatively small in the VTA as well as in the nucleus accumbens when compared with the response in the PFC. It is concluded that DA released from mesocortical neurons can be modulated by two different mechanisms: first, by glutamate afferents to the VTA that modify the nerve-impulse flow of DA neurons; and, second, by glutamate afferents to the PFC that act at the level of the DA nerve terminals. The behaviour context (arousal or stress versus hypotension) determines which type of interaction predominates.

Topics: Animals; Dopamine; Excitatory Amino Acid Antagonists; Glutamic Acid; Handling, Psychological; Hypotension; Male; Microdialysis; Nitroprusside; Nucleus Accumbens; Piperazines; Prefrontal Cortex; Presynaptic Terminals; Quinoxalines; Rats; Rats, Wistar; Receptors, Glutamate; Receptors, N-Methyl-D-Aspartate; Ventral Tegmental Area