Jun 1, 2012

An allosteric enhancer of M₄ muscarinic acetylcholine receptor function inhibits behavioral and neurochemical effects of cocaine

Ditte DenckerAnders Fink-Jensen


The mesostriatal dopamine system plays a key role in mediating the reinforcing effects of psychostimulant drugs like cocaine. The muscarinic M₄ acetylcholine receptor subtype is centrally involved in the regulation of dopamine release in striatal areas. Consequently, striatal M₄ receptors could be a novel target for modulating psychostimulant effects of cocaine. For the first time, we here addressed this issue by investigating the effects of a novel selective positive allosteric modulator of M₄ receptors, VU0152100, on cocaine-induced behavioral and neurochemical effects in mice. To investigate the effect of VU0152100 on the acute reinforcing effects of cocaine, we use an acute cocaine self-administration model. We used in vivo microdialysis to investigate whether the effects of VU0152100 in the behavioral studies were mediated via effects on dopaminergic neurotransmission. In addition, the effect of VU0152100 on cocaine-induced hyperactivity and rotarod performance was evaluated. We found that VU0152100 caused a prominent reduction in cocaine self-administration, cocaine-induced hyperlocomotion, and cocaine-induced striatal dopamine increase, without affecting motor performance. Consistent with these effects of VU0152100 being...Continue Reading

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  • Citations19


Mentioned in this Paper

Motor Performance
Behavior, Animal
Lentiform Nucleus Structure
Cocaine Dependence
Synaptic Transmission
Gene Deletion Abnormality

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