Panel a: areas of the core and shell divisions of the nucleus accumbens +2.0 mm from bregma marked in gray that were sampled at the end of the reinstatement session 2 hours after an i.p. injection of 10 mg/kg of cocaine. Panel b: examples of Fos positive nuclei in the shell of the nucleus accumbens +2.0 from bregma (Fos-positive nuclei are labeled green). At the start of the second reinstatement session rats were given an i.p injection of saline or 10 mg/kg of cocaine and brains obtained 2 hours later. The panels are from rats that had a history of cocaine self-administration, with cocaine delivered over 5 sec or 90 sec, and controls that received an i.p. injection of saline (Sal) or an acute (first time) injection of cocaine (Acute Coc). The shell division sampled within the nucleus accumbens is indicated by the white ellipse. Scale bar indicates 100 microns. Panel c: the mean (+SEM) number of Fos positive nuclei in the nucleus accumbens (+2.0 mm from bregma) core and shell subdivisions two hours after an i.p. injection of cocaine (10 mg/kg) in rats with a history of cocaine self-administration, when cocaine was delivered i.v. over 5, 45 or 90 sec. Control rats with no history of cocaine self-administration were given an i.p. injection of either saline (S) or cocaine for the first time (C). This test was conducted 45 days after the last self-administration session. In the NAc shell, a cocaine priming injection produced greater Fos expression compared to the saline control group in all groups except the 5 sec group (45 sec, p<0.004; 90 sec, p<0.007; acute cocaine control group, p<0.008). The 45, 90 sec and acute cocaine groups did not differ from each other, and these groups all showed significantly greater Fos expression than the 5 sec group (5 sec vs. 45 sec, p<0.028; vs. 90 sec, p<0.047; vs. acute cocaine control, p=0.059). In the NAc core, only the 45 sec (p<0.001), 90 sec (p<0.02) and acute cocaine group (p<0.02) had greater Fos expression compared to the saline control group, The 5 sec group did not have greater Fos expression than saline control (p>0.05), and had significantly fewer Fos positive cells than all other groups given cocaine priming injections (p’s<0.02).