Figure 2.

Influence of PZM21 on addiction‐like behaviour in mice. (a) In contrast to morphine (10 mg·kg⁻¹, i.p.), PZM21 (20, 40, and 80 mg·kg⁻¹, i.p.) did not induce a preference towards drug‐associated compartment in a CPP test at any of the tested doses. (b) Repeated treatment with morphine induced locomotor sensitization and expression, whereas that effect was not observed after PZM21 administration. Mice treated with 80 mg·kg⁻¹ PZM21 presented a slight expression of sensitization after an 8‐day incubation period. (c) Chronic administration of PZM21 (80 mg·kg⁻¹, but not 20 or 40 mg·kg⁻¹) as well as morphine induced naloxone‐precipitated jumps, considered as a physical sign of withdrawal. (d) Repeated treatment with 40 and 80 mg·kg⁻¹ PZM21 resulted in a decrease of antinociceptive efficacy of the compound. Tolerance was assessed using tail flick test performed on each experimental day, 1 hr after the drug administration. Data are presented as the mean ± SEM. In (a, c), * P<.05, PZM21‐ and morphine‐treated groups significantly different from saline controls; in (b, d) within group effects significantly different from the first day of experiment. # P < .05, expression of locomotor sensitization within groups significantly different from the last day of sensitization development. Numbers of animals used in experiments presented in Table S5. CPP, conditioned place preference; Morph, morphine; MPE, maximum possible effect; Sal, saline