ABSTRACT
The present study investigated the role of several 5-HT receptor subtypes in the lateral parabrachial nucleus (LPBN) in the control of sodium appetite (i.e. NaCl consumption). Male Holtzman rats had cannulas implanted bilaterally into the LPBN for the injection of 5-HT receptor agonists and antagonists in conjunction with either acute fluid depletion or 24-h sodium depletion. Following these treatments, access to 0.3 M NaCl was provided and the intakes of saline and water were measured for the next 2 h. Bilateral injections of the 5-HT2A receptor antagonist, ketanserin or the 5-HT2C receptor antagonist, mianserin into the LPBN increased 0.3 M NaCl intake without affecting water intake induced by acute fluid-depletion. Bilateral injections of the 5-HT2B receptor agonist, BW723C86 hydrochloride, had no effect on 0.3 M NaCl or water intake under these conditions. Treatment of the LPBN with the 5-HT2B/2C receptor agonist, 2-(2-methyl-4-clorophenoxy) propanoic acid (mCPP) caused dose-related reductions in 0.3 M NaCl intake after 24 h sodium depletion. The effects of mCPP were prevented by pretreating the LPBN with the 5-HT2B/2C receptor antagonist, SDZSER082. Activation of 5-HT3 receptors by the receptor agonist, 1-phenylbiguanide (PBG) caused dose-related increases in 0.3 M NaCl intake. Pretreatment of the LPBN with the 5-HT3 receptor antagonist, 1-methyl-N-[8-methyl-8-azabicyclo (3.2.1)-oct-3-yl]-1H-indazole-3-carboxamide (LY-278,584) abolished the effects of PBG, but LY-278,584 had no effects on sodium or water intake when injected by itself. PBG injected into the LPBN did not alter intake of palatable 0.06 M sucrose in fluid replete rats. The results suggest that activation of the 5-HT2A and 5-HT2C receptor subtypes inhibits sodium ingestion. In contrast, activation of the 5-HT3 receptor subtype increases sodium ingestion. Therefore, multiple serotonergic receptor subtypes in the LPBN are implicated in the control of sodium intake, sometimes by mediating opposite effects of 5-HT. The results provide new information concerning the control of sodium intake by LPBN mechanisms.
Subject(s)
Drinking Behavior/physiology , Pons/metabolism , Receptors, Serotonin, 5-HT2/physiology , Receptors, Serotonin, 5-HT3/physiology , Sodium Chloride/metabolism , Animals , Behavior, Animal , Dose-Response Relationship, Drug , Drinking/drug effects , Drinking Behavior/drug effects , Drug Interactions , Ketanserin/pharmacology , Male , Models, Biological , Pons/drug effects , Rats , Serotonin Antagonists/pharmacology , Serotonin Receptor Agonists/pharmacologyABSTRACT
Serotonin [5-hydroxytryptamine (5-HT)] and CCK injected into the lateral parabrachial nucleus (LPBN) inhibit NaCl and water intake. In this study, we investigated interactions between 5-HT and CCK into the LPBN to control water and NaCl intake. Male Holtzman rats with cannulas implanted bilaterally in the LPBN were treated with furosemide + captopril to induce water and NaCl intake. Bilateral LPBN injections of high doses of the 5-HT antagonist methysergide (4 microg) or the CCK antagonist proglumide (50 microg), alone or combined, produced similar increases in water and 1.8% NaCl intake. Low doses of methysergide (0.5 microg) + proglumide (20 microg) produced greater increases in NaCl intake than when they were injected alone. The 5-HT(2a/2c) agonist 2,5-dimetoxy-4-iodoamphetamine hydrobromide (DOI; 5 microg) into the LPBN reduced water and NaCl intake. After proglumide (50 microg) + DOI treatment, the intake was not different from vehicle treatment. CCK-8 (1 microg) alone produced no effect. CCK-8 combined with methysergide (4 microg) reduced the effect of methysergide on NaCl intake. The data suggest that functional interactions between 5-HT and CCK in the LPBN may be important for exerting inhibitory control of NaCl intake.
Subject(s)
Appetite/physiology , Intralaminar Thalamic Nuclei/physiology , Serotonin/pharmacology , Sincalide/analogs & derivatives , Sincalide/pharmacology , Sodium, Dietary , Amphetamines/pharmacology , Animals , Appetite/drug effects , Drug Interactions , Homeostasis , Intralaminar Thalamic Nuclei/drug effects , Male , Methysergide/administration & dosage , Methysergide/pharmacology , Microinjections , Models, Neurological , Neurons/drug effects , Neurons/physiology , Proglumide/pharmacology , Rats , Rats, Sprague-Dawley , Serotonin/administration & dosage , Serotonin Receptor Agonists/pharmacology , Sincalide/administration & dosageABSTRACT
It has been shown that the serotonergic mechanisms of the lateral parabrachial nucleus (LPBN) inhibit NaCl intake in different models of angiotensin II (ANG II)-dependent NaCl intake in rats. However, there is no information about the involvement of LPBN serotonergic mechanisms on NaCl intake in a model of NaCl intake not dependent on ANG II like deoxycorticosterone (DOCA)-induced NaCl intake. Therefore, in this study we investigated the effects of bilateral injections of serotonergic agonist and antagonist into the LPBN on DOCA-induced 1.8% NaCl intake in rats. Male Holtzman rats were treated with s.c. DOCA (10 mg/rat each every 3 days). After a period of training, in which the rats had access to 1.8% NaCl during 2 h for several days, the rats were implanted with stainless steel cannulas bilaterally into the LPBN. Bilateral injections of the serotonergic receptor antagonist methysergide (4 microg/0.2 microl each site) in the LPBN increased 1.8% NaCl intake (32.2+/-3.9 versus vehicle: 15.0+/-1.6 ml/2 h, n=10) and water intake (12.5+/-3.5 versus vehicle: 3.2+/-1.0 ml/2 h). Injections of the serotonergic 5HT(2A/2C) receptor agonist DOI (5 microg/0,2 microl each site) in the LPBN reduced 1.8% NaCl intake (6.8+/-1.7 versus saline: 12.4+/-1. 9 ml/2 h, n=10) and water intake (2.2+/-0.8 versus saline: 4.4+/-1.0 ml/2 h). Besides the previously demonstrated importance for the control of ANG II-dependent water and NaCl intake, the data show that the serotonergic inhibitory mechanisms of the LPBN are also involved in the control of DOCA-induced NaCl intake.
Subject(s)
Amphetamines/pharmacology , Cerebellar Nuclei/physiology , Desoxycorticosterone/pharmacology , Drinking Behavior/physiology , Feeding Behavior/physiology , Methysergide/pharmacology , Serotonin Receptor Agonists/pharmacology , Serotonin/physiology , Sodium, Dietary , Amphetamines/administration & dosage , Animals , Blood Pressure/drug effects , Cerebellar Nuclei/drug effects , Desoxycorticosterone/administration & dosage , Drinking Behavior/drug effects , Feeding Behavior/drug effects , Heart Rate/drug effects , Male , Methysergide/administration & dosage , Microinjections , Rats , Rats, Sprague-DawleyABSTRACT
In the present study, we investigated the effect of previous injection of either prazosin (alpha 1-adrenergic antagonist) or atropine (muscarinic cholinergic antagonist) into the medial septal area (MSA) on the pressor and dipsogenic response induced by intracerebroventricular (ICV) injection of carbachol (cholinergic agonist) and angiotensin II (ANGII) in rats. The pressor and dipsogenic responses to ICV carbachol (7 nmol) were reduced after previous treatment of the MSA with atropine (0.5 to 5 nmol), but not prazosin (20 and 40 nmol). The dipsogenic response to ICA ANGII (25 ng) was reduced after prazosin (40 nmol) into the MSA. The pressor response to ICV ANGII was not changed either by previous treatment of the MSA with prazosin or atropine. The present results suggest a dissociation among the pathways subserving the control of dipsogenic and pressor responses to central cholinergic or angiotensinergic activation.
