Differential effects of caffeine on the antidepressant-like effect of amitriptyline in female rat subpopulations with low and high immobility in the forced swimming test.

The interaction of caffeine (1 mg/kg) and amitriptyline (15 mg/kg) on the immobility time (IT) during Porsolt's forced swimming test (FST) was investigated in female Wistar rats. Akaike's Information Criterion indicated that the ITs recorded from 142 rats during the first day of the FST followed a bimodal distribution. Hence, the median (125.5 s) was used to classify the animals in subpopulations with low (<125.5 s, LI-rats) or high (>125.5 s, HI-rats) immobility. The paired t-test was used to compare the change of ITs between the first and second swimming sessions. Vehicle-treated animals had a significant increase of ITs during the second day of the test, either in LI-rats (77+/-12 s vs. 196+/-8 s, P<0.0001, n=6) or HI-rats (150+/-8 s vs. 201+/-10 s, P<0.02, n=6). In LI-rats amitriptyline only prevented the increase of ITs during the second session (74+/-27 s vs. 97+/-42 s, n=12), whereas in HI-rats the antidepressant produced a significant decrease of ITs during the second session (161+/-22 s vs. 118+/-32 s, n=7, P<0.02). While caffeine alone prevented the increase of ITs in both groups, the methylxanthine abolished the effect of amitriptyline in HI-rats (165+/-23 s vs. 165+/-46 s, n=9), leaving the antidepressant action unaffected in LI-rats (87+/-23 s vs. 96+/-58 s, n=9). These results suggest that the anti-immobility effect of amitriptyline in HI-rats is mediated in part by endogenous adenosine.