Effect of the 5-HT(6) serotonin antagonist MS-245 on the actions of (-)nicotine.
The 5-HT(6) serotonin receptor antagonist MS-245 neither substitutes for nor antagonizes the discriminative stimulus effects of (-)nicotine. However, MS-245 was shown to enhance the potency of (-)nicotine in Sprague-Dawley rats trained to discriminate 0.6 mg/kg of (-)nicotine from saline vehicle in a typical two-lever drug discrimination paradigm such that a combination of MS-245 (5.0 mg/kg) plus the ED(50) dose of (-)nicotine caused the animals to respond as if they had received the training dose of (-)nicotine. MS-245 also potentiated the hypolocomotor actions, but not the antinociceptive effects, of (-)nicotine in mice. The results suggest possible involvement of serotonin-regulated signaling mechanisms in certain behavioral effects of nicotine.
Young
Richard
R
Department of Medicinal Chemistry, School of Pharmacy, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA 23298-0540, USA.
Bondareva
Tatiana
T
Wesolowska
Anna
A
Young
Shawquia
S
Glennon
Richard A
RA
D000818:Animals; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects; D009538:Nicotine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects*; D014363:Tryptamines / Q000494:pharmacology*
C419803:N1-benzenesulfonyl-5-methoxy-N,N-dimethyltryptamine; D011985:Receptors, Serotonin; D014363:Tryptamines; C097216:serotonin 6 receptor; D009538:Nicotine