The mediating role of phosphodiesterase type 4 in the dopaminergic modulation of motor impulsivity.

The mediating role of phosphodiesterase type 4 in the dopaminergic modulation of motor impulsivity. Behav Brain Res. 2018 May 17;: Authors: Heckman PRA, Blokland A, Van Goethem NP, Van Hagen BTJ, Prickaerts J Abstract The current study investigated the mediating role of phosphodiesterase type 4 (PDE4) regulated cAMP in the dopaminergic modulation of premature responding (action restraint) in rats. Response inhibition, which includes action restraint, finds its neurobiological origin in cortico-striatal-thalamic circuitry and can be modulated by dopamine. Intracellularly, the effect of dopamine is largely mediated through the cAMP/PKA signaling cascade. Areas in the prefrontal cortex are very sensitive to their neurochemical environment, including catecholamine levels. As a result, we investigated the effects of intracellular modulation of the dopamine cascade by means of PDE4 inhibition by roflumilast on premature responding in a hypo, normal and hyper dopaminergic state of the brain. As a hypo dopaminergic model we induced a 6-OHDA lesion in the (rat) prefrontal cortex, more specifically the infralimbic cortex. For the hyper dopaminergic state we also turned to a well-established model of impaired action restraint, namely the systemic administration of d-amphetamine. In line with the notion of a U-shaped relation between dopamine and impulsive responding, we found that both increasing and decreasing dopamine levels resulted in an in...
Source: Behavioural Brain Research - Category: Neurology Authors: Tags: Behav Brain Res Source Type: research