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Biol Psychiatry. 2008 Jan 15;63(2):207-13. Epub 2007 Jul 12.

Increased expression of 5-HT6 receptors in the nucleus accumbens blocks the rewarding but not psychomotor activating properties of cocaine.

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Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, Washington, USA.



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.


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.


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.


These results demonstrate that 5-HT6Rs in the NAc can selectively modulate drug reward, possibly through facilitation of reward learning.

[Indexed for MEDLINE]

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