Chronic clozapine, but not haloperidol, treatment affects rat brain vesicular monoamine transporter 2.
We compared the effect of chronic clozapine and haloperidol treatment on the expression of rat brain vesicular monoamine transporter (VMAT(2)) as well as on the membranal presynaptic transporters for serotonin, dopamine and noradrenaline. Rats were treated for 21 days with clozapine (25 mg/kg), haloperidol (0.5 mg/kg) or saline. VMAT(2) expression was assessed on the protein level by high affinity [3H]dihydrotetrabenazine binding using autoradiography, and on the mRNA level by in situ hybridization. The densities of the monoamine transporters were evaluated by autoradiography using specific ligands. Clozapine administration led to an increase in [3H]TBZOH binding in the nucleus accumbens, prefrontal cortex and striatum, whereas haloperidol had no effect on VMAT(2) binding capacity. The clozapine-induced increase in VMAT(2) was accompanied by a parallel increase in the membrane serotonin transporter in the prefrontal cortex and the striatum. Haloperidol induced an increase in the serotonin transporter in the striatum and the core of the nucleus accumbens. The special effect of clozapine on VMAT(2) expression may be relevant to its unique therapeutic advantages.
Rehavi
Moshe
M
Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel. mrehavi@post.tau.ac.il
Roz
Netta
N
Weizman
Abraham
A
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001665:Binding Sites / Q000187:drug effects; D001692:Biological Transport / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D001923:Brain Chemistry / Q000235:genetics; D003024:Clozapine / Q000494:pharmacology*; D004334:Drug Administration Schedule; D005473:Fluoxetine / Q000031:analogs & derivatives* / Q000378:metabolism; D006220:Haloperidol / Q000494:pharmacology*; D017403:In Situ Hybridization; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D026901:Membrane Transport Proteins; D009479:Neuropeptides; D017374:Paroxetine / Q000378:metabolism; D010879:Piperazines / Q000378:metabolism; D051381:Rats; D013747:Tetrabenazine / Q000031:analogs & derivatives* / Q000378:metabolism; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins
D014150:Antipsychotic Agents; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009479:Neuropeptides; D010879:Piperazines; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins; D005473:Fluoxetine; C011386:nisoxetine; C032811:dihydrotetrabenazine; D017374:Paroxetine; C044630:1-(2 (diphenylmethoxy)ethyl)-4-(3-phenylpropyl)piperazine; D003024:Clozapine; D006220:Haloperidol; D013747:Tetrabenazine