Fig. 1.

Rats (n = 24) received continuous and intermittent access to a caffeine solution in a 24 h two-bottle choice paradigm. The remaining control rats (n = 12) were experimentally naive and received no caffeine throughout the experiment. The rats were first tested to establish a caffeine dose-response curve using four different concentrations of caffeine (0.07, 0.14, 0.3, and 0.7 mg/mL). The optimal concentration (0.3 mg/mL), based on the dose response, was used for the subsequent experiments. After the dose-response test, the rats received continuous access to caffeine for 8 days. After continuous access, the rats received intermittent access (every other day) to caffeine for 10 total sessions over 3 weeks. During intermittent access, all of the rats were tested for irritability-like behavior and pain sensitivity 24 h after the last access to caffeine. The rats were then returned to continuous access to caffeine for 8 days and then tested for compulsive-like caffeine intake with the quinine adulteration test.