Chronic cocaine treatment alters dendritic arborization in the adult motor cortex through a CB1 cannabinoid receptor–dependent mechanism

The CB1 cannabinoid receptors modulate the addictive processes associated with different drugs of abuse, including psychostimulants. Mice lacking CB1 receptors exhibit an important attenuation of the reinforcing responses produced by cocaine in an operant self-administration paradigm. We have investigated the effect of chronic cocaine treatment on dendrite structure and spine density of the principal cortical neuron, the pyramidal neuron, in CB1 knockout mice and wild type littermates. Layer III pyramidal cells of the motor cortex were injected intracellularly in fixed cortical slices and their morphometric parameters analyzed. Under basal conditions, the field area of the dendritic arbors was more extensive and dendritic spine density was higher in wild type mice than in CB1 knockout mice. Chronic treatment of cocaine diminished the size and length of the basal dendrites and spine density on pyramidal cells from wild type mice. However, the total number of spines in the pyramidal cells of CB1 knockout mice augmented slightly following chronic cocaine treatment, although no changes in the morphology of the dendritic arbor were observed. Our data demonstrate that microanatomy and synaptic connectivity are affected by cocaine, the magnitude and nature of these changes depend on the presence of CB1 receptors.