Figure 2: Effects of chronic stress before or after repeated cocaine exposure.
From: Role of dopamine D2 receptors in plasticity of stress-induced addictive behaviours
(a–e) Initiation of sensitization to cocaine (n=16–20 mice per group). (a) Experimental protocol. Sal, saline; Coc, cocaine. (b) Total locomotor counts during 30 min after injection of saline or cocaine (15 mg kg−1, i.p.). (c) Locomotor counts averaged for the five test sessions (cocaine effect F1,65=262.78, P<0.0001). (d) Locomotor activity after the first (day1, C1) and last (day5, C5) injections of cocaine (cocaine day effect F1,54=29.76, P<0.0001; genotype effect F1,54=95.39, P<0.0001). (e) C5/C1 ratio of locomotor counts (cocaine day effect F1,54=27.4, P<0.0001; genotype × cocaine day interaction F1,54=3.9, P=0.0533). (f–i) Effect of chronic stress on initiation of sensitization to cocaine (n=5–8 mice per group). Mice were examined as in a through e with the addition that they were subjected to restraint stress (St) or not (NSt) for 2 h per day for 14 days before the initiation protocol. (h) For both genotypes, cocaine effect F1,20>40.73, P<0.0001. (i) For both genotypes, cocaine effect F1,16>5.93, P<0.03; cocaine × stress interaction F1,16<0.2, P>0.66. (j–l) Effect of chronic stress on expression of sensitization to cocaine (n=4–11 mice per group). (j) Experimental protocol. (k, l) Locomotor activity of WT (k) and D2R–/– (l) mice during the initiation of behavioural sensitization with five daily injections of cocaine (15 mg kg−1) as well as during the expression of behavioural sensitization induced by challenge with cocaine (10 mg kg−1, i.p.) after drug withdrawal for 14 days with or without stress (each saline versus cocaine pretreatment group two-tailed Student’s t-test, P<0.01; expression of sensitization on day 22: (k) stress × cocaine interaction F1,12=4.27, P=0.0610 and (l) cocaine effect F1,16=47.5, P<0.0001). Two-tailed Student’s t-test for b and g: *P<0.05, **P<0.01, ***P<0.001. Two-way analysis of variance post hoc test for c, d e, h and i, as well as the expression of sensitization in k and l: *P<0.05, **P<0.01, ***P<0.001 versus the value for C1; ###P<0.001 versus saline control; †P<0.05 versus WT mice; &P<0.05 versus NSt value. All data are means±s.e.m.
