Chronic amphetamine treatment reduces NGF and BDNF in the rat brain.
Amphetamines (methamphetamine and d-amphetamine) are dopaminergic and noradrenergic agonists and are highly addictive drugs with neurotoxic effect on the brain. In human subjects, it has also been observed that amphetamine causes psychosis resembling positive symptoms of schizophrenia. Neurotrophins are molecules involved in neuronal survival and plasticity and protect neurons against (BDNF) are the most abundant neurotrophins in the central nervous system (CNS) and are important survival factors for cholinergic and dopaminergic neurons. Interestingly, it has been proposed that deficits in the production or utilization of neurotrophins participate in the pathogenesis of schizophrenia. In this study in order to investigate the mechanism of amphetamine-induced neurotoxicity and further elucidate the role of neurotrophins in the pathogenesis of schizophrenia we administered intraperitoneally d-amphetamine for 8 days to rats and measured the levels of neurotrophins NGF and BDNF in selected brain regions by ELISA. Amphetamine reduced NGF levels in the hippocampus, occipital cortex and hypothalamus and of BDNF in the occipital cortex and hypothalamus. Thus the present data indicate that chronic amphetamine can reduce the levels of NGF and BDNF in selected brain regions. This reduction may account for some of the effects of amphetamine in the CNS neurons and provides evidences for the role of neurotrophins in schizophrenia.
Angelucci
Francesco
F
Karolinska Institutet, Clinical Neuroscience, Psychiatry M56, Karolinska University Hospital Huddinge, SE-14186 Stockholm, Sweden.
Gruber
Susanne H M
SH
El Khoury
Aram
A
Tonali
Pietro Attilio
PA
Mathé
Aleksander A
AA
D000661:Amphetamine / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects*; D008297:Male; D020932:Nerve Growth Factor / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D019208:Brain-Derived Neurotrophic Factor; D000697:Central Nervous System Stimulants; D020932:Nerve Growth Factor; D000661:Amphetamine