DREADDs to deconstruct cocaine actions

Additionally, using designer receptors exclusively activated by designer drugs (DREADDs) technology, we found that stimulation of the serotonergic dorsal raphe nucleus (DRN) afferents to the nucleus accumbens (NAc) abolishes cocaine reward and promotes anti-depressive-like behaviors. Lastly, using a rat model of compulsive-like cocaine self-administration, we found that inhibition of dorsal raphe 5-HT1Aautoreceptors attenuates cocaine self-administration in rats with 6h extended access, but not 1 hour access to the drug. Therefore, our findings suggest an important role for 5-HT1A autoreceptors, and thus DRNNAc 5-HT neuronal activity, in the etiology and vulnerability to cocaine reward and addiction. Moreover, our findings support a strategy for antagonizing 5-HT1A autoreceptors for treating cocaine addiction.

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