Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.492050
Title: Midbrain projections to the prefrontal cortex and nucleus accumbens : the anatomical basis of their regulation by serotonin
Author: Qian, Xiao-xiao
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2007
Availability of Full Text:
Full text unavailable from EThOS.
Please contact the current institution’s library for further details.
Abstract:
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.
Supervisor: Not available Sponsor: Not available
Qualification Name: University of Oxford, 2007 Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.492050  DOI: Not available
Share: