Effects of selective serotonin and dopamine agonists on plasma levels of glucose, insulin and glucagon in the rat.
Male Sprague-Dawley rats were given one of the 5-HT receptor agonists 8-OH-DPAT (0.5-2.0 mg kg-1), TFMPP (0.125-2.0 mg kg-1), DOI (0.125-2.0 mg kg-1), and m-CPBG (1.25-20.0 mg kg-1), selective for 5-HT1A, 5-HT1B, 5-HT2 and the 5-HT3 receptors, respectively, or one of the DA receptor agonists bromocriptine (2.0-32.0 mg kg-1), quinpirole (0.5-8.0 mg kg-1) and 7-OH-DPAT (0.2-3.2 mg kg-1), selective for DA D2, DA D2/D3 and DA D3 receptors, respectively. An additional group of animals was given buspirone (2.0-8.0 mg kg-1) a 5-HT1A receptor agonist and DA D2 receptor antagonist. Separate groups of rats were given both the 5-HT1A receptor antagonist pindolol and 8-OH-DPAT or both the DA D2/D3 receptor antagonist raclopride and 7-OH-DPAT. Blood samples were collected 30 min (in some cases 120 min) after drug administration and assayed for insulin, glucagon and glucose levels. The 5-HT1A receptor agonist 8-OH-DPAT produced a statistically significant decrease in plasma insulin levels and an increase in glucose, whereas glucagon levels were unaffected. The only effect observed after buspirone treatment was a small increase in plasma glucose levels. No significant effects on plasma insulin, glucagon or glucose were seen after treatment with the 5-HT1B, 5-HT2 or 5-HT3 agonists. The DA D3 receptor agonist 7-OH-DPAT produced a decrease in plasma insulin (3.2 mg kg-1, 120 min) and an increase in glucose levels. Administration of the DA D2/D3 receptor agonist quinpirole resulted only in increased plasma glucose, whereas the DA D2 receptor agonist bromocriptine had no effect. In support of a separate mediation of glucose secretion by 5-HT1A and DA D3 receptors, the effects of 8-OH-DPAT on glucose levels were antagonized by (-)pindolol pretreatment, and the 7-OH-DPAT-induced effects on glucose levels were antagonized by raclopride pretreatment. It is concluded that plasma glucose levels are under separate serotonergic and dopaminergic control, exerted via 5-HT1A and DA D3 receptors, respectively.
Uvnäs-Moberg
K
K
Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.
Ahlenius
S
S
Alster
P
P
Hillegaart
V
V
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D001971:Bromocriptine / Q000494:pharmacology; D002065:Buspirone / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology*; D004873:Ergolines / Q000494:pharmacology; D005934:Glucagon / Q000097:blood*; D007328:Insulin / Q000097:blood*; D008297:Male; D019257:Quinpirole; D051381:Rats; D017207:Rats, Sprague-Dawley; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
D001786:Blood Glucose; D018491:Dopamine Agonists; D004873:Ergolines; D007328:Insulin; D017366:Serotonin Receptor Agonists; D013764:Tetrahydronaphthalenes; D019257:Quinpirole; D001971:Bromocriptine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D005934:Glucagon; C031349:7-hydroxy-2-N,N-dipropylaminotetralin; D002065:Buspirone