Changes in Dopaminergic and GABAergicExpression of the Olfactory Bulb in Mouseafter Acute or Chronic Amphetamine Treatment

• Main Authors: Pei-Jung Cheng, 鄭珮容
• Other Authors: 尹相姝
• Format: Others
• Language: zh-TW
• Published: 2007
• Online Access: http://ndltd.ncl.edu.tw/handle/61772756021516797752

碩士 === 臺灣大學 === 解剖學暨生物細胞學研究所 === 95 === The olfactory bulb (OB) contained dopaminergic and GABAergic neurons and may play important roles in affective disorders. Amphetamine (Amph) treated animals have been used as models to study pathogenesis of addiction and schizophrenia. Previous work using animal model has demonstrated that chronic administration of Amph alters the expression of tyrosine hydroxylase (TH)、glutamic acid decarboxylase (GAD) and phosphorylated CREB (pCREB )in neocortex, striatum, hippocampus of the rat. In addition, calcium-binding proteins (CaBPs) were useful markers of some populations of GABAergic neurons in the central nervous system. Thus, this study investigated the role of olfactory bulb plays in the mechanisms for the action of acute and chronic Amph treatment, by examining the expression of TH, AADC, GAD67, CaBPs and pCREB. In this study, male adult mice were received single or multiple (2 doses/day, 7 doses in total) intraperitoneal injections of saline or Amph, 5mg/kg. At 0.5 or 4 h after the last injection, the mice were perfused with Bouin’s fixative, followed by preparation of paraffin OB sections and immunohistochemistry. Our results revealed that： (1)At 0.5 h after chronic Amph treatments, the number of TH-positive somata and the ratio of cell processes were increased in the glomerular layer (GL). (2)At 0.5 h and 4h after acute and chronic Amph treatment, AADC-immunoreactivity (IR) was unchanged in all layer of OB. (3) At 0.5 h and 4 h after acute Amph treatment, the number of GAD67-positive somata was increased in the external plexiform layer (EPL). At 0.5h after chronic Amph treatments, the ratio of GAD67-positive terminals was increased in all layers. At 4 h after chronic Amph treatments, the number of GAD67-positive somata was decreased in the GL and granule cell layer (GrL), and the ratio of GAD67-positive terminals was decreased in all layers. (4) At 0.5 and 4 h after acute Amph treatment, the number of PV-positive somata and the ratio of cell processes were significantly increased in the EPL. (5) At 4 h after acute Amph treatment, the number of CR-positive somata was significantly increased in all layers. (6) At 0.5 after acute Amph treatment, the number of pCREB-positive glia was increased in the GL, and the number of pCREB-positive neurons was increased in the GrL. At 4 h after chronic Amph treatments, the number of pCREB-positive neurons was decreased in the GrL. The results of double-staining： (1) At 0.5 h after chronic saline and Amph treatments, about 59% or 72% TH- positive somata were GAD67-IR in the GL. About 53% or 62% GAD67-somata were TH-IR in the GL. (2) After acute saline and Amph treatment, all the PV-positive somata contained GAD67-IR in the EPL. At 0.5 h after saline and Amph treatment, about 31% or 56% GAD67-somata contained PV-IR in the EPL. At 4 h after saline and Amph treatment, about 39% or 49% GAD67-somata contained PV-IR in the EPL. (3) At 4 h after acute saline and Amph treatments, about 16% or 40% CR-positive somata were GAD67-IR in the EPL. About 36% or 68% GAD67-somata were CR-IR in the EPL. Some of CR-somata were GAD67-IR in the ML and GrL. (4) In the GrL, at 4 h after chronic Amph treatments, some pCREB-expression cells were surrounded by GAD67-terminals. Some pCREB-expression cells showed GAD67 in their cytoplasm. Our results suggested that up-regulation of TH and GAD67 at 0.5 h after chronic Amph treatments could imply compensation to long-term depletion of GABA and dopamine by Amph. The acute Amph induced increase in PV and CR expression may indicate inhibitory regulation of the OB to the stimulation of the psychostimulant. Changes in the expression of pCREB may be induced by activation or inhibition of protein kinase A, CaM or MAPK pathway. The data supported that amphetamine induces changes in neurotransmitter systems and neuronal activity in the OB, leading to olfactory functional changes, and may implicate early mechanisms of pathogenesis of psychosis.