Contrasting changes in extracellular dopamine and glutamate along the rostrocaudal axis of the anterior cingulate cortex of the rat following an acute d-amphetamine or dopamine challenge.

There is evidence for functional specificity of subregions along the rostrocaudal axis of the anterior cingulate cortex (ACC). The subregion-specific distribution of dopaminergic afferents and glutamatergic efferents along the ACC make these obvious candidates for coding such regional responses. We investigated this possibility using microdialysis in freely-moving rats to compare changes in extracellular dopamine and glutamate in the rostral ('rACC': Cg1 and Cg3 (prelimbic area)) and caudal ('cACC': Cg1 and Cg2) ACC induced by systemic or local administration of d-amphetamine. Systemic administration of d-amphetamine (3 mg/kg, i.p.) caused a transient increase in extracellular dopamine in the rACC, but an apparent increase in the cACC of the same animals was less clearly defined. Local infusion of d-amphetamine increased dopamine efflux in the rACC, only. Glutamate efflux in the rACC was increased by local infusion of dopamine (5-50 µM), which had negligible effect in the cACC, but only systemic administration of d-amphetamine increased glutamate efflux and only in the cACC. The asymmetry in the neurochemical responses within the rACC and cACC, to the same experimental challenges, could help explain why different subregions are recruited in the response to specific environmental and somatosensory stimuli and should be taken into account when studying the regulation of neurotransmission in the ACC. This article is part of the Special Issue entitled 'CNS Stimulants'.

Neurochemical changes in a double transgenic mouse model of Alzheimer's disease fed a pro-oxidant diet.

Oxidative stress is implicated in the pathogenesis of Alzheimer's disease (AD) causing neurodegeneration and decreased monoamine neurotransmitters. We investigated the effect of administration of a pro-oxidant diet on the levels of monoamines and metabolites in the brains of wildtype and transgenic mice expressing mutant APP and PS-1 (TASTPM mice). Three-month-old TASTPM and wildtype (C57BL6/J) mice were fed either normal or pro-oxidant diet for 3 months. The neocortex, cerebellum, hippocampus and striatum were assayed for their monoamine and monoamine metabolite content using HPLC with electrochemical detection. Striatal tyrosine hydroxylase (TOH) levels were analysed by Western blotting. In the striatum, female TASTPM mice had higher levels of DOPAC and male TASTPM mice had higher levels of 5-HIAA compared to wildtype mice. Administration of pro-oxidant diet increased striatal MHPG, turnover of NA and 5-HT levels in female TASTPM mice compared to TASTPM mice fed control diet. The pro-oxidant diet also decreased DOPAC levels in female TASTPM mice compared to those fed control diet. Striatal TOH did not depend on diet, gender or genotype. In the neocortex, the TASTPM genotype increased levels of 5-HIAA in male mice fed control diet compared to wildtype mice. In the cerebellum, the TASTPM genotype led to decreased levels of HVA (male mice only) and also decreased turnover of DA (female mice only) compared to wildtype mice. These data suggest a sparing of monoaminergic neurones in the cortex, striatum and hippocampus of TASTPM mice fed pro-oxidant diet and could be indicative of increased activity in corticostriatal circuits. The decreased cerebellar levels of HVA and turnover of DA in TASTPM mice hint at possible axonal degeneration within this subregion.