Co-release of noradrenaline and dopamine from noradrenergic neurons in the cerebral cortex induced by clozapine, the prototype atypical antipsychotic

Abstract

The results suggest that clozapine, by inhibiting alpha(2)-adrenoceptors, co-releases DA and NA from noradrenergic terminals in the occipital cortex and that the same mechanism might be responsible for the concomitant increase of the two monoamines in the mPFC.

Noradrenaline transporter blockers raise extracellular dopamine in medial prefrontal but not parietal and occipital cortex: differences with mianserin and clozapine

“…However, direct comparison of these observations with the present ones is made difficult by the fact that whereas in the present study the same concentric probes with a 3 mm dialysing surface were utilized, in the study by Devoto et al (2003) the two probes were different not only in geometry but also in dialysing surface (8 mm for the transcerebral OccCX probes and 4 mm for the concentric PFCX probes). As a result of this, while in our study dialysate values of DA and NA in the different cortical areas are directly comparable, in the study of Devoto et al (2003) comparison of dialysate DA and NA in the PFCX and OccCX required normalization to unitary membrane length. This approach, however, fails to take into account differences in the recovery of DA from the extracellular compartment of the PFCX and OccCX due to the different probe geometry and non-linear behaviour of transmitter recovery by microdialytic membranes (Bungay et al 2001).…”

“…The same also applied to the higher dose of clozapine in the ParCX. An increase of dialysate DA in the OccCX has been recently reported by Devoto et al (2003). Given the potent a 2 receptor blocking properties of clozapine and mianserin, the increase of DA induced by these drugs in the ParCX and OccCX can be accounted for by relief of the release of DA from an inhibitory tone exerted by endogenous NA through a 2 receptors.…”

“…Therefore, the differences between our observations and those of Devoto et al (2001) can be accounted for by the lower overall density of the DA innervation of the laterally placed frontal cortical areas assayed by their microdialysis probes. Indeed, more recently, the same group (Devoto et al 2003), utilizing concentric probes in the PFCX and transcerebral probes in the OccCX, has reported a small difference (29%) in basal DA in dialysates from the two areas. However, direct comparison of these observations with the present ones is made difficult by the fact that whereas in the present study the same concentric probes with a 3 mm dialysing surface were utilized, in the study by Devoto et al (2003) the two probes were different not only in geometry but also in dialysing surface (8 mm for the transcerebral OccCX probes and 4 mm for the concentric PFCX probes).…”

“…Indeed, more recently, the same group (Devoto et al 2003), utilizing concentric probes in the PFCX and transcerebral probes in the OccCX, has reported a small difference (29%) in basal DA in dialysates from the two areas. However, direct comparison of these observations with the present ones is made difficult by the fact that whereas in the present study the same concentric probes with a 3 mm dialysing surface were utilized, in the study by Devoto et al (2003) the two probes were different not only in geometry but also in dialysing surface (8 mm for the transcerebral OccCX probes and 4 mm for the concentric PFCX probes). As a result of this, while in our study dialysate values of DA and NA in the different cortical areas are directly comparable, in the study of Devoto et al (2003) comparison of dialysate DA and NA in the PFCX and OccCX required normalization to unitary membrane length.…”

Dopamine Depletion of the Prefrontal Cortex Induces Dendritic Spine Loss: Reversal by Atypical Antipsychotic Drug Treatment

“…Acute and chronic treatments with atypical APDs such as olanzapine increase extracellular levels of dopamine in the PFC, while typical APDs such as haloperidol do not (Youngren et al, 1994;Li et al, 1998). The ability of atypical APDs to increase cortical dopamine levels has been attributed in part to their antagonism of a 2 autoreceptors, leading to activation of noradrenergic neurons and the subsequent release of dopamine from cortical noradrenergic axons (Li et al, 1998;Devoto et al, 2003). When the firing rate of noradrenergic neurons is increased, as occurs with olanzapine (Dawe et al, 2001), dopamine-b-hydroxylase rather than tyrosine hydroxylase becomes the rate-limiting (Scatton et al, 1983).…”