Changes in Proenkephalin mRNA expression in forebrain areas after amphetamine-induced behavioural sensitization.
Acute and repeated psychostimulant administration induces a long-lasting enhanced behavioural response to a subsequent drug challenge, known as behavioural sensitization. This phenomenon involves persistent neurophysiological adaptations, which may lead to drug addiction. Brain dopaminergic pathways have been implicated as the main neurobiological substrates of behavioural sensitization, although other neurotransmitters and neuromodulators may also participate. In order to investigate a possible involvement of opioid systems in amphetamine (AMPH) behavioural sensitization, we studied the AMPH-induced changes in Proenkephalin (Pro-Enk) mRNA expression in forebrain areas in both drug-naïve and AMPH-sensitized rats. Male Sprague-Dawley rats were sensitized to AMPH by means of a single AMPH (1 mg/kg s.c.) injection and the same dose was injected 7 days later to assess the expression of sensitization. Pro-Enk mRNA levels were evaluated by in situ hybridization in coronal brain sections. AMPH injection induced an increase in Pro-Enk mRNA expression in the nucleus accumbens and the medial-posterior caudate-putamen in drug-naïve rats. Challenge with AMPH to rats injected 1 week earlier with AMPH induced motor sensitization and increased and decreased Pro-Enk mRNA expression in the prefrontal cortex and the anterior medial caudate-putamen, respectively. Our results suggest that alterations in cortical and striatal enkephalinergic systems could contribute to the expression of AMPH behavioural sensitization.
Morales-Mulia
Marcela
M
Departamento de Neuroquímica, Subdirección de Investigaciones Clínicas, Instituto Nacional de Psiquiatría Ramón de la Fuente, Calzada México Xochimilco 101, Col. San Lorenzo Huipulco, 14370 México D.F., Mexico.
Panayi
Fany
F
Lambás-Señas
Laura
L
Scarna
Hélène
H
Méndez
Milagros
M
D000818:Animals; D001345:Autoradiography; D001522:Behavior, Animal / Q000187:drug effects*; D002421:Caudate Nucleus / Q000187:drug effects / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003913:Dextroamphetamine / Q000494:pharmacology*; D004745:Enkephalins / Q000096:biosynthesis* / Q000502:physiology; D017403:In Situ Hybridization; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D016548:Prosencephalon / Q000378:metabolism*; D011498:Protein Precursors / Q000096:biosynthesis*; D011699:Putamen / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000502:physiology
D000697:Central Nervous System Stimulants; D004745:Enkephalins; D011498:Protein Precursors; D012333:RNA, Messenger; C029992:proenkephalin; D003913:Dextroamphetamine