Nicotine withdrawal: a behavioral assessment using schedule controlled responding, locomotor activity, and sensorimotor reactivity.
Three different behavioral measures were used to assess the effects of abrupt cessation of chronic nicotine treatment. Nicotine (0, 3, or 6 mg/kg per day) was continuously administered for 12 days in rats by surgically implanting Alzet osmotic mini-pumps subcutaneously. Experiment 1 employed a light/dark discrimination task. There were no significant effects on number of responses or percent correct responding either during nicotine administration, or following cessation of nicotine. Experiment 2 examined ambulatory (locomotor) and nonambulatory activity. Chronic nicotine administration produced significant dose-dependent increases in both ambulatory and nonambulatory activity during the first 3 days of exposure. However, no significant alterations were seen in activity levels following nicotine cessation. Experiment 3 examined sensorimotor reactivity using the auditory startle response. During nicotine withdrawal, significant increases were seen in startle amplitude in both nicotine groups for 4 days. Nicotine (0.4 mg/kg, IP) administered before startle testing during the withdrawal phase attenuated the increased reactivity seen during nicotine cessation. These studies indicate that 1) rats display increased sensorimotor reactivity after cessation of chronic nicotine exposure, and 2) the expression of nicotine dependence and withdrawal is dependent on the behavioral task employed.
Lilly Research Laboratories, Eli Lilly and Company, Greenfield, IN 46140.
D R
DR
Helton
D L
DL
Modlin
J P
JP
Tizzano
K
K
Rasmussen
D000161:Acoustic Stimulation; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003216:Conditioning, Operant / Q000187:drug effects*; D007260:Infusion Pumps; D008027:Light; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D009538:Nicotine / Q000008:administration & dosage / Q000009:adverse effects*; D051381:Rats; D013216:Reflex, Startle / Q000187:drug effects*; D012055:Reinforcement Schedule; D012646:Self Administration; D013375:Substance Withdrawal Syndrome / Q000523:psychology*
D009538:Nicotine