Diagram of the experimental design for alternating measurement of intracranial self-stimulation (ICSS) and locomotion in mice habituated to saline injections (days 1–6) and given a repeated cocaine regimen (days 8–18) followed by withdrawal (days 19–32) and cocaine challenge. For example, Group A mice received saline and ICSS was measured on Day 1; received saline and locomotion was measured on Day 2; etc. ICSS mice (Groups A and B) received saline and ICSS was measured every other day during cocaine withdrawal (days 19–32). Cocaine challenge (15 mg/kg i.p.) was measured in half of Group A and Group B mice with ICSS on day 33 and with locomotor activity on day 34; the other half were challenged with locomotion measurement (day 33) then ICSS (day 34). Solid grey lines (days 7, 9, etc.) indicate experimental days that mice remained in their home cages. Days numbered in bold (days 8, 10, etc.) indicate experiments in which mice received cocaine. Numbers in parentheses on day 7 indicate mice removed from the protocol for protein determinations shown in Figure 3. See Materials and Methods for details.