Alterations in BDNF and phospho-CREB levels following chronic oral nicotine treatment and its withdrawal in dopaminergic brain areas of mice

• Published in: Neuroscience letters Vol. 491; no. 2; pp. 108 - 112
• Main Authors: Kivinummi, Tanja, Kaste, Kristiina, Rantamäki, Tomi, Castrén, Eero, Ahtee, Liisa
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 17.03.2011; Elsevier
• Subjects: Administration, Oral; Animals; BDNF; Biological and medical sciences; Brain - drug effects; Brain - metabolism; Brain-Derived Neurotrophic Factor - metabolism; Cyclic AMP Response Element-Binding Protein - metabolism; Dopamine - metabolism; Enzyme-Linked Immunosorbent Assay; Fundamental and applied biological sciences. Psychology; Immunohistochemistry; Male; Mice; Neuronal Plasticity - drug effects; Nicotine; Nicotine - administration & dosage; Nicotinic Agonists - administration & dosage; pCREB; Phosphorylation; Substance Withdrawal Syndrome - metabolism; Tobacco Use Disorder - metabolism; Vertebrates: nervous system and sense organs; NAc; VTA; BDNF; pCREB; Nicotine; Dopamine; Rodentia; Central nervous system; Catecholamine; Encephalon; Vertebrata; Chronic; Mammalia; Mouse; Animal; Neurotransmitter; Brain derived neurotrophic factor; Transcription factor CREB
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2011.01.015

▶ Withdrawal from chronic nicotine induces long-lasting increase in BDNF levels. ▶ Nicotine changed BDNF levels in the NAc, in the VTA, and in the substantia nigra. ▶ Nicotine and its withdrawal oppositely affected pCREB in the NAc and in the VTA. ▶ Withdrawal from nicotine reversed the effect on pCREB in the NAc and in the VTA. Neuronal changes induced by chronic nicotine in the brain dopaminergic circuits are thought to lead to compulsive nicotine use. When nicotine is given to mice chronically in their drinking water, its intake and effects mimic human smoking. Previously, we have reported that this treatment in mice induces several neurochemical and behavioural changes that are associated with nicotine addiction. Here we studied the effects of chronic oral nicotine treatment and nicotine treatment cessation on two well-characterised markers of neuronal plasticity, brain-derived neurotrophic factor (BDNF) and phosphorylated cAMP-responsive element-binding protein (pCREB), in several dopaminergic brain areas. BDNF levels were not altered by chronic nicotine treatment, but they were significantly increased in the nucleus accumbens (NAc) after 24 h and 29 days of nicotine abstinence and in the ventral tegmental area (VTA) and substantia nigra after 29 days of nicotine abstinence. These findings suggest that nicotine abstinence promotes long-lasting neuroadaptations in dopaminergic neurocircuits by inducing BDNF production. Withdrawal from chronic nicotine treatment oppositely affected pCREB levels in the NAc and in the VTA. Thus, in the NAc, the pCREB levels were significantly elevated and in the VTA significantly decreased as compared with the pCREB levels during the nicotine treatment. These alterations could be compensatory and related to increased dopaminergic signalling during nicotine treatment. In conclusion, the current results suggest the involvement of BDNF- and CREB-related neuronal processes in nicotine-induced neurochemical, behavioural, and neuroplastic changes in dopaminergic neurocircuits.