Stimulation of the ventral tegmental area enhances the effect of vasopressin on blood pressure in conscious rats.
The mesolimbic dopamine system projects to a large number of forebrain areas and plays an important role in the regulation of locomotor activity, cognition and reward. We previously found evidence for a functional interaction between the mesolimbic dopamine system and circulating vasopressin and the present study was performed to test the hypothesis that mesolimbic dopamine stimulation modulates the cardiovascular effects of vasopressin. Sprague-Dawley rats were stereotaxically implanted with a guide cannula into the region of origin of the mesolimbic system, the ventral tegmental area, and instrumented with catheters into the abdominal aorta and jugular vein. One week later, separate groups of conscious rats were injected intravenously with 1, 3 or 10 ng kg(-1) of arginine-vasopressin or other vasopressor drugs before and after intra-ventral tegmental area injection of 10 nmol of neurotensin. Intra-ventral tegmental area injections of neurotensin had no significant effect on mean arterial pressure and heart rate but significantly potentiated the pressor response to intravenous administration of vasopressin when compared to saline-injections. However, the vasopressin-induced bradycardia was unaffected. Intravenous pretreatment with raclopride blocked the ability of neurotensin, injected into the ventral tegmental area, to potentiate the vasopressin-induced pressor response. Intra ventral tegmental area injections of neurotensin had no effect on the pressor response and bradycardia induced by intravenous angiotensin II or methoxamine. In conclusion, these results suggest that the mesolimbic dopamine system, in addition to its well-known role in the regulation of behaviour, modulates cardiovascular control by potentiating the effects of vasopressin on mean arterial pressure. British Journal of Pharmacology (2000) 129, 29 - 36
van Den Buuse
M
M
Neuropharmacology Laboratory, Baker Medical Research Institute, Melbourne, Australia. m.vandenbuuse@papyrus.mhri.edu.au
Catanzariti
R
R
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D008845:Microinjections; D009496:Neurotensin / Q000008:administration & dosage / Q000494:pharmacology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D051381:Rats; D017207:Rats, Sprague-Dawley; D013238:Stereotaxic Techniques; D013268:Stimulation, Chemical; D013373:Substance P / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014667:Vasopressins / Q000378:metabolism / Q000494:pharmacology*; D017557:Ventral Tegmental Area / Q000502:physiology*
D010446:Peptide Fragments; D014662:Vasoconstrictor Agents; D014667:Vasopressins; D000804:Angiotensin II; D013373:Substance P; D009496:Neurotensin; C032720:substance P (5-11), pGlu(5)-MePhe(8)-MeGly(9)-; D008729:Methoxamine; D011761:Pyrrolidonecarboxylic Acid