Reinstatement and spontaneous recovery of previously extinguished nico
tine-taking behavior were examined in rats. Male subjects were trained
to self-administer nicotine (30 mu g/kg per infusion, IV; one 60-min
session per day for 3 weeks). Extinction sessions were then given for
5-10 days during which saline was substituted for nicotine. Subsequent
ly, in the first set of tests for nicotine seeking, the reinstatement
of lever presses that previously delivered nicotine was examined after
priming injections of saline and nicotine (75, 150 and 300 mu g/kg, S
C; and 30 and 60 mu g/kg, IV). In the second set of tests for nicotine
-seeking, rats were tested after an additional 21-day drug-free period
during which they were not exposed to the self-administration chamber
s (a test for the spontaneous recovery of drug seeking), and after pri
ming injections of nicotine (150 and 300 mu g/kg, SC). Reinstatement o
f extinguished food-reinforced behavior after exposure to nicotine was
also determined. Priming injections of nicotine reinstated nicotine s
eeking regardless of the route of administration. In addition, previou
sly extinguished nicotine seeking recovered spontaneously after a 21-d
ay period during which. rats were not exposed to the drug-taking envir
onment, Nicotine also reinstated extinguished food-reinforced behavior
in rats with a history of nicotine self-administration, but not in dr
ug-naive rats. The present results extend previous work with opioid an
d stimulant drugs on reinstatement of drug seeking by the self-adminis
tered drug, It also appears that, as with other positive reinforcers,
the mere passage of time is a sufficient condition for the spontaneous
recovery of extinguished nicotine seeking.