BACKGROUND: Repeated exposure to cocaine produces enduring forms of drug experience-dependent behavioral plasticity, including conditioned place preference (CPP) and psychomotor sensitization, a progressive and persistent increase in cocaine's psychomotor activating effects. Although serotonin-6 receptors (5-HT6Rs) are abundantly expressed in the brain regions thought to underlie these phenomena, such as the nucleus accumbens (NAc), surprisingly little is known about the role of 5-HT6Rs in the rewarding and psychomotor activating effects of cocaine. METHODS: Viral-mediated gene transfer was used to selectively increase 5-HT6R expression in the NAc of rats. The effects of 5-HT6R overexpression and the selective 5-HT6R antagonist Ro4368554 on CPP and psychomotor sensitization were examined. RESULTS: Increased expression of 5-HT6Rs in the NAc blocks a CPP to cocaine but has no effect on either the acute locomotor response to cocaine or on the development of cocaine-induced locomotor sensitization. Furthermore, antagonism of 5-HT6Rs facilitates the acquisition of a CPP to cocaine but has no effect on cocaine-induced stereotypy. CONCLUSIONS: These results demonstrate that 5-HT6Rs in the NAc can selectively modulate drug reward, possibly through facilitation of reward learning.
BACKGROUND: Repeated exposure to cocaine produces enduring forms of drug experience-dependent behavioral plasticity, including conditioned place preference (CPP) and psychomotor sensitization, a progressive and persistent increase in cocaine's psychomotor activating effects. Although serotonin-6 receptors (5-HT6Rs) are abundantly expressed in the brain regions thought to underlie these phenomena, such as the nucleus accumbens (NAc), surprisingly little is known about the role of 5-HT6Rs in the rewarding and psychomotor activating effects of cocaine. METHODS: Viral-mediated gene transfer was used to selectively increase 5-HT6R expression in the NAc of rats. The effects of 5-HT6R overexpression and the selective 5-HT6R antagonist Ro4368554 on CPP and psychomotor sensitization were examined. RESULTS: Increased expression of 5-HT6Rs in the NAc blocks a CPP to cocaine but has no effect on either the acute locomotor response to cocaine or on the development of cocaine-induced locomotor sensitization. Furthermore, antagonism of 5-HT6Rs facilitates the acquisition of a CPP to cocaine but has no effect on cocaine-induced stereotypy. CONCLUSIONS: These results demonstrate that 5-HT6Rs in the NAc can selectively modulate drug reward, possibly through facilitation of reward learning.
Authors: Matthew Brodsky; Adam J Lesiak; Alex Croicu; Nathalie Cohenca; Jane M Sullivan; John F Neumaier Journal: Brain Res Date: 2017-01-10 Impact factor: 3.252
Authors: Atom J Lesiak; Matthew Brodsky; Nathalie Cohenca; Alexandra G Croicu; John F Neumaier Journal: Mol Pharmacol Date: 2018-04-20 Impact factor: 4.436
Authors: Linda D Simmler; Allison M J Anacker; Michael H Levin; Nina M Vaswani; Paul J Gresch; Alex G Nackenoff; Noelle C Anastasio; Sonja J Stutz; Kathryn A Cunningham; Jing Wang; Bing Zhang; L Keith Henry; Adele Stewart; Jeremy Veenstra-VanderWeele; Randy D Blakely Journal: Br J Pharmacol Date: 2017-07-11 Impact factor: 8.739