Decreased limbic vesicular monoamine transporter 2 in a genetic rat model of depression.
Psychopharmacological and neurochemical research suggests that alterations in monoamine transporters may be involved in the etiology of depression. We studied the expression of the brain-type vesicular monoamine transporter (VMAT2) in the Flinders sensitive line (FSL) rats, which represent a genetic animal model for clinical depression in humans. VMAT2 expression at the protein level was assessed by autoradiography using [(3)H]dihydrotetrabenazine ([(3)H]TBZOH) binding, in the prefrontal cortex, the striatum and its subregions, nucleus accumbens (NAC), ventral tegmental area (VTA) and the substantia nigra pars compacta (SNC). The VMAT2 mRNA level was analyzed by in situ hybridization, in the VTA, SNC and the dorsal raphe (DR) nucleus. Reduced levels of [(3)H]TBZOH binding were detected in the striatum and its subregions, NAC shell but not in the NAC core. A marked reduction of 21% was found in the VTA while only a slight reduction (13%) was observed in the SNC. The reduced levels of VMAT2 protein binding capacity were not accompanied by a parallel alteration in VMAT2 mRNA levels in the VTA, the SNC and the DR. Since the VMAT2 is responsible for the intracellular storage and regulated release of monoamines, the reduced [(3)H]TBZOH binding levels in limbic brain regions of FSL rats may imply a reduced density of vesicular monoamine transporters, which can result in reduced monoamine transmission. Such reduction in the limbic neurotransmission, especially in NAC shell and VTA regions, may be involved in the depressive features of anhedonia and lack of motivation reported in the FSL rats.
Schwartz
Karin
K
Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 69978, Israel.
Yadid
Gal
G
Weizman
Abraham
A
Rehavi
Moshe
M
D000818:Animals; D003863:Depression / Q000235:genetics* / Q000378:metabolism*; D004195:Disease Models, Animal; D008032:Limbic System / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D026901:Membrane Transport Proteins; D009479:Neuropeptides; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013747:Tetrabenazine / Q000031:analogs & derivatives* / Q000378:metabolism; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins
D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009479:Neuropeptides; D012333:RNA, Messenger; C493454:Slc18a2 protein, rat; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins; C032811:dihydrotetrabenazine; D013747:Tetrabenazine