Inhibition of CREB activity in the dorsal portion of the striatum potentiates behavioral responses to drugs of abuse

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Abstract
The striatum participates in multiple forms of behavioral adaptation, including habit formation, other forms of procedural memory, and short- and long-term responses to drugs of abuse. The cyclic-AMP response element binding protein (CREB) family of transcription factors has been implicated in various forms of behavioral plasticity, but its role in the dorsal portion of the striatum-has been little explored. We previously showed that in transgenic mice in which CREB function is inhibited in the dorsal striatum, bidirectional synaptic plasticity and certain forms of long-term procedural memory are impaired. Here we show, in startling contrast, that inhibition of striatal CREB facilitates cocaine- and morphine-place conditioning and enhances locomotor sensitization to cocaine. These findings propose CREB as a positive regulator of dorsal striatum-dependent procedural learning but a negative regulator of drug-related learning.