The 5-HT3 receptor partial agonist MD-354 (meta-chlorophenylguanidine) enhances the discriminative stimulus actions of (+)amphetamine in rats.
The effect of the 5-HT3 receptor partial agonist MD-354 (meta-chlorophenylguanidine) was examined on the discriminative stimulus produced by (+)amphetamine. Using male Sprague-Dawley rats trained to discriminate 1.0 mg/kg (i.p.) of (+)amphetamine from saline vehicle (VI 15-s schedule of reinforcement) in a two-lever operant procedure for appetitive reward, tests of stimulus generalization (substitution) and antagonism showed that MD-354 neither substituted for, nor antagonized, the amphetamine stimulus at the doses evaluated. Administration of (+)amphetamine doses in combination with a fixed (i.e., 1.0 mg/kg) dose of MD-354 shifted the (+)amphetamine dose-response curve to the left such that, following 0.3 mg/kg of (+)amphetamine, stimulus generalization occurred. Furthermore, MD-354 doses of 0.1, 0.3 and 1.0 mg/kg, but not doses of 0.01, 0.5, 1.5 or 3.0 mg/kg (i.p.), administered in combination with the ED(50) dose (0.33 mg/kg) of (+)amphetamine resulted in stimulus generalization (i.e., >80% drug-appropriate responding). It is concluded that even though MD-354 lacks amphetamine-like central stimulant actions of its own it can modulate the discriminative stimulus effects of (+)amphetamine in rats.
Dukat
Małgorzata
M
Department of Medicinal Chemistry School of Pharmacy Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia 23298-0540, United States.
Wesolowska
Anna
A
Young
Richard
R
Glennon
Richard A
RA
D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003913:Dextroamphetamine / Q000494:pharmacology*; D004193:Discrimination Learning; D004192:Discrimination, Psychological / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005795:Generalization, Stimulus / Q000187:drug effects; D006146:Guanidines / Q000494:pharmacology*; D008297:Male; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D058827:Serotonin 5-HT3 Receptor Agonists; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D000697:Central Nervous System Stimulants; D006146:Guanidines; D058827:Serotonin 5-HT3 Receptor Agonists; D017366:Serotonin Receptor Agonists; C495409:m-chlorophenylguanidine; D003913:Dextroamphetamine