Assessment of Dopaminergic and Serotonergic Receptor Antagonists in Male Rats Trained to Discriminate 4-Methylmethcathinone (Mephedrone)
Date of Award
Master of Arts
Dr. Lisa Baker
Dr. Alan Poling
Dr. Ron Van Houten
Drug discrimination, mephedrone, synthetic cathinone, serotonin, dopamine
Masters Thesis-Open Access
Preclinical drug discrimination studies of the synthetic cathinone, 4-methylmethcathinone (mephedrone) have demonstrated its effects are comparable to those of other popular psychostimulant drugs. Few studies have directly examined the contribution of specific neurotransmitter receptors to mephedrone’s discriminative stimulus effects. The present study investigated the role of dopamine and serotonin receptors in these effects. Eight adult male Sprague-Dawley rats were trained to discriminate 3.0 mg/kg mephedrone from saline. After dose-response curves were determined with mephedrone (0.375-3.0 mg/kg), a series of stimulus antagonism tests were conducted with dopamine antagonists (Sch 23390, haloperidol) and serotonin antagonists (WAY 100,635, MDL 100,907, pirenperone) administered as a pretreatment with each mephedrone dose. Attenuation of mephedrone discrimination by Sch 23390 and haloperidol implicates the involvement of both D1 and D2 dopamine receptors in these effects. Partial attenuation of discrimination by MDL 100,907 and pirenperone, but not WAY 100,635, indicates 5HT2 receptors also contribute to these effects, while 5HT1A receptors do not. The absence of full stimulus antagonism with these compounds indicate mephedrone’s discriminative stimulus effects may be mediated by a combination of monoamine receptors or other neurotransmitter actions yet to be evaluated. These results contribute to a growing body of literature regarding the interoceptive stimulus effects of mephedrone and serve to inform clinical science regarding the neurochemical mechanisms involved with abuse risks of this substance.
Burroughs, Rachel L., "Assessment of Dopaminergic and Serotonergic Receptor Antagonists in Male Rats Trained to Discriminate 4-Methylmethcathinone (Mephedrone)" (2020). Masters Theses. 5176.