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. 2014 Mar 7;8:70. doi: 10.3389/fnbeh.2014.00070

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Copyright © 2014 Howell, Monk, Carmack, Mrowczynski, Clark and Anagnostaras.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Continuous ZIP administration blocks cocaine-induced locomotor sensitization. (A) Depiction of the procedure used in experiment 1 (n = 10 Veh/Coc, n = 11 ZIP/Coc, n = 7 Veh/Veh, n = 8 ZIP/Veh). Mice were implanted with osmotic pumps, filled such that ZIP would be delivered ICV just prior to the first cocaine administration session and terminate 24 h following the sixth session (10 nmol, 0.25 μL/h). Animals underwent six cocaine administration sessions (2 sessions per day) during which time the development and expression of sensitization was assessed. (B) ZIP impaired the development of sensitization. The data represent the average distance traveled for each session (±s.e.m.). The distance traveled by mice receiving ZIP/Coc was reduced compared to mice treated with Veh/Coc across the six cocaine administration sessions [15 mg/kg, i.p.; MANOVA, F_{(3, 32)} = 18.3, p < 0.001; Fisher's PLSD p < 0.05]. ZIP alone did not produce any locomotor attenuating effects (ZIP/Veh, Veh/Veh, p = 0.93). (C) ZIP did not alter the acute response to cocaine (session 1). Distance traveled at each minute of the session (±s.e.m.) is shown. Animals receiving cocaine (ZIP/Coc, Veh/Coc) traveled a greater distance compared to mice receiving vehicle (ZIP/Veh, Veh/Veh, p < 0.05), but there was no difference between the cocaine-treated groups (p = 0.78). (D) ZIP/Coc mice showed reduced locomotor sensitization compared to Veh/Coc mice during session 6 [ANOVA, F_{(3, 32)} = 16.7, p < 0.001; ZIP/Coc, Veh/Coc Fisher's PLSD p < 0.05]. Distance traveled at each minute of the session (±s.e.m.) is shown. ZIP alone did not produce any effects on locomotor activity. (E) Sensitization, measured as the difference between the sensitized (session 6) and acute (session 1) responses, was blocked in ZIP/Coc mice. The average difference in distance traveled (±s.e.m.) is shown for each group. Sensitization in ZIP/Coc mice did not differ from mice treated with ZIP/Veh or Veh/Veh (p > 0.1). (F) Sensitization was also assessed while all animals were off-ZIP. ZIP/Coc and Veh/Coc groups showed greater activity than mice that previously received vehicle [ZIP/Veh, Veh/Veh; MANOVA, F_{(3, 32)} = 3.2, p < 0.05]. Animals in the ZIP/Coc group showed reduced sensitization compared to animals that had previously received Veh/Coc during the first 5 min of the test [ANOVA, F_{(3, 32)} = 10.373, p < 0.001; Fisher's PLSD, ZIP/Coc vs. Veh/Coc, p < 0.05]. There were no differences in the acute response to cocaine between animals that had not previously received cocaine (Fisher's PLSD, Veh/Veh, ZIP/Veh, p = 0.96).