Chronic quinpirole exposure.

A) The striatum consists for 95% out of medium spiny GABAergic neurons which branch out in a number of dendrites. On the heads of the dendrites, glutamatergic neurons connect that are often coming from the cortical regions. This then results in downstream signalling. This signalling can be modified and altered by DA-ergic neurons connecting on the branches. In the normal condition a balanced system is in place whereby release of DA will trigger postsynaptic D1 and D2 receptors. These G-coupled receptors will determine the amount of conversion from ATP to cAMP, a secondary messenger which affects downstream signalling. The triggering of the presynaptic D2-receptors results in a feedback mechanism by inhibition of tyrosine hydroxylase, responsible for the conversion of L-tyrosine to L-DOPA eventually leading to Dopamine. Likewise, the D2-receptors present on the glutamatergic neuron inhibit glutamate release which will reduce downstream signalling and further DA-release. DAT transporters participate in the reuptake of DA present in the synapse. B) A different scenario takes place when, due to constant stimulation of the D2-receptor, the receptor becomes sensitized. This will increase the inhibition on the release of DA as well as glutamate, leading to less release of both neurotransmitters. However, due to the constant activation of the D2R receptor a process called heterologous sensitization occurs whereby the consistent activation of Gαi/o-coupled receptors results in a compensatory increase in adenylyl cyclase. This will result in a D2-mediated activation of the D1-pathway resulting in the displayed motor behaviour.