Lithium-induced polydipsia: dependence on nigrostriatal dopamine pathway and relationship to changes in the renin-angiotensin system.
The dependence of lithium-induced polydipsia (LIP) on central monoamine pathways was investigated using several pharmacological manipulations. Intracisternal administration of 6-hydroxydopamine (6-OHDA) in combination with pargyline or desipramine was used to deplete dopamine (DA), norepinephrine, or both catecholamines. Significant decreases in LIP were seen after treatments that depleted brain DA, whereas depletion of norepinephrine alone did not affect LIP. Site-specific injection of 6-OHDA into the substantia nigra or caudate nucleus, but not the nucleus accumbens or noradrenergic dorsal bundle, also caused a decrease in LIP. Depletion of serotonin by intracisternal administration of 5,7-dihydroxytryptamine also had no effect on LIP. Consistent with these findings, the DA receptor blocker haloperidol attenuated LIP. Thus, LIP appears to be dependent on intact nigrostriatal DA fibers, but not on other monoaminergic systems in the brain. Lithium also increased plasma renin activity (PRA) and angiotensin I and II immunoreactivity in plasma, though the time course of LIP onset did not directly parallel these latter changes in the renin-angiotensin axis. Neither the PRA or angiotensin II immunoreactivity in lithium-treated animals was sufficiently high to account for LIP. In addition, the 6-OHDA lesions of the caudate nucleus or substantia nigra that attenuated LIP did not affect the lithium-induced increases in PRA or in angiotensin I or II concentrations. Thus, LIP probably involves mechanisms other than just being a direct response to lithium-induced increases in PRA or angiotensin II concentration and simply may not be secondary to lithium-induced polyuria. Because of the similar pharmacological characteristics of angiotensin II and lithium-induced drinking, a role for angiotensin receptors in LIP cannot be ruled out.
D000804:Angiotensin II / Q000097:blood; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D002395:Catecholamines / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects*; D004298:Dopamine / Q000502:physiology*; D004327:Drinking Behavior / Q000187:drug effects* / Q000502:physiology; D006892:Hydroxydopamines / Q000494:pharmacology; D008094:Lithium / Q000494:pharmacology*; D008297:Male; D009434:Neural Pathways / Q000187:drug effects; D016627:Oxidopamine; D051381:Rats; D011919:Rats, Inbred Strains; D012084:Renin-Angiotensin System / Q000187:drug effects*; D013378:Substantia Nigra / Q000187:drug effects*
D002395:Catecholamines; D006892:Hydroxydopamines; D000804:Angiotensin II; D016627:Oxidopamine; D008094:Lithium; D004298:Dopamine