Nicotine withdrawal leads to increased sensitivity of serotonergic neurons to the 5-HT1A agonist 8-OH-DPAT.
In order to explore the neurophysiology of nicotine withdrawal, we examined the activity of serotonergic neurons in the dorsal raphe nucleus in rats undergoing withdrawal from chronic exposure to nicotine. Animals were exposed to nicotine (6 mg/kg per day base) via SC implanted osmotic minipumps. After 12 days the pumps were removed and the animals allowed to go through spontaneous withdrawal. Rats were anesthetized on various days of the procedure and the effect of the 5-hydroxytryptamine (5-HT)-1A agonist 8-OH-DPAT on the single-unit activity of serotonergic neurons in the dorsal raphe nucleus was examined. The sensitivity of serotonergic neurons to 8-OH-DPAT was not changed by the chronic administration of nicotine or saline; slightly increased on day 2 of withdrawal; significantly increased on days 3 and 4 of withdrawal; and no longer significantly increased by day 7 of withdrawal. These results indicate that serotonergic neurons in the dorsal raphe nucleus have an increased sensitivity to systemically administered 8-OH-DPAT in rats undergoing nicotine withdrawal and that the serotonergic system may play a role in the symptoms of nicotine withdrawal.
Rasmussen
K
K
Lilly Research Laboratories, Eli Lilly & Co., Lilly Corporate Center, Indianapolis, IN 46285, USA. rasmussen_kurt@lilly.com
Czachura
J F
JF
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology*; D000818:Animals; D004594:Electrophysiology; D008297:Male; D009474:Neurons / Q000187:drug effects*; D009538:Nicotine / Q000009:adverse effects*; D018722:Nicotinic Agonists / Q000009:adverse effects*; D011903:Raphe Nuclei / Q000166:cytology / Q000187:drug effects; D051381:Rats; D012701:Serotonin / Q000502:physiology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*
D018722:Nicotinic Agonists; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D009538:Nicotine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin