NICOTINE WITHDRAWAL LEADS TO INCREASED FIRING RATES OF MIDBRAIN DOPAMINE NEURONS

IN order to explore the neurophysiology of nicotine withdrawal, we exa mined the activity of substantia nigra (A9) and ventral tegmental area (A10) dopamine cells in rats undergoing withdrawal from chronic expos ure to nicotine. Animals were exposed to nicotine (6 mg kg(-1) day(-1) base) via s.c. implanted osmotic minipumps. After 12 days the pumps w ere removed and the animals allowed to go through spontaneous withdraw al. Rats were anesthetized on various days of the procedure and single -unit recordings were made from A9 and A10 dopamine cells. Chronic adm inistration of nicotine led to a decreased firing rate of A10, but not A9, dopamine cells. Upon withdrawal from the chronic exposure to nico tine, the firing rates of A10 dopamine cells returned to control level s, while the firing rate of A9 dopamine cells significantly increased above control levels. This increased dopamine neuronal activity may pl ay a role in some behavioural symptoms of nicotine withdrawal.