Locomotor Sensitization.

Locomotor chamber apparatus was placed under a video tracking system (Any-maze, Stoelting) and measurements were made automatically by the software. Mice were habituated to experimenter handling and injections (i.p.) over a 2-d period, followed by five consecutive once-daily injections of saline or morphine. Initial studies characterizing morphine effects on plasticity involved administration of 10 or 20 mg/kg (Fig. S1 B and C), with a dose of 10 mg/kg used for all subsequent sensitization experiments, as it produced a maximal effect on AMPAR/NMDAR ratios. For all test days, animals were habituated to testing chambers for 30 min and motor activity was monitored for 90–180 min following drug or saline administration. Following the final day of drug treatment (saline, morphine), animals were returned to their home cage for 10–14 d. For experiments involving ceftriaxone (Fig. 2 A–G and Fig. S2 A–C), mice received 7–10 daily injections (i.p.) of either vehicle (saline) or ceftriaxone (400 mg/kg, i.p) beginning ∼72 h following the final drug treatment. Mice were killed for electrophysiological recordings within 10–14 d of the final drug treatment and within 24–48 h of the final abstinence treatment (vehicle, ceftriaxone).

Previous studies demonstrated that administration of ceftriaxone (200 mg/kg) in rats is sufficient to block drug-seeking behavior (24, 39). In the present study, a dose of 400 mg/kg was chosen using an allometric scaling calculator to estimate interspecies dosage scaling between rats and mice using exponential allometry.