Midbrain projections to the prefrontal cortex and nucleus accumbens : the anatomical basis of their regulation by serotonin

• Main Author: Qian, Xiao-xiao
• Published: University of Oxford 2007
• Subjects: 615.1
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.492050

Atypical antIpsychotic drugs (APDs) improve negative symptoms and cognitive impairmtlnts in schizophrenia, without producing motol' side tlffects, possibly due to their action on serotonin (5HT) rectlplurs. 5·HTzA and 5-HTzc receptors are considertld of particular relevance to schizophrenia and localized the ventral tegmental area (VTA) dopamillergic neurons, but whether they are localiz.ed on mesocortical and mesoaccumbens neurons remains unclear. The VTA receives serotonergic inputs from both the dorsal and median raphe nuclei (DRN I MRN), but the pattern of scrotonergic regulation on VTAcells is unknown. The origins of the VTA projections to the prefrontal cortex (PFC) and nucleus accumbens (NAcb) were examined using retrograde tracers FluoroGold (FG), cholera toxin (eTb-Au), and neurobiotin (NB). Fullowing paired retrograde tracers injected into the pre and NAcb, the VTA projection neurons were imlllunolabelled with eilhcr t.lupaminergic or GABAergic murker, tyrosine hydroxlyase (TH) or glutamic acid decarboxylase (GAD) 65/67, to detennine the neurobiochemical profiles. Mesocortical and mcsoaccumbens neurons were found largely segregated and mainly dopaminergic. To study the interaction between serotonergic and dopaminergic systems in the VTA, I exumined the distribution pattern of 5-HT2A receptors using immunohistochemical methods and results showed that this receptor was localized preferentially in proximal dendrites, with some labelling of cell bodies. Furthermore, more than one-third ofthe mesocortical and l11esoaccumbens neurons were found colocalized with 5-HT2A receptor immunoreactivity. The origin of the serotonergic innervation of mesoaccumbcns neurons was examined. By injecting the anterograde tracer biotinylaled dextran amine (BOA) into the DRN or MRN and FG into the NAcb, and examining their relationship in the VTA. Although, anterogrudely labelled raphe terminals were found in close proximity to cells retrogradely labelled with Fa, no direct synaptic contacts were found, supporting the hypothesis of the paracrine neurotransmission of 5HT in the midbrain.