Background Some epidemiological and cessation studies suggest physical exercise attenuates or prevents recreational drug use in humans. Preclinical studies indicate wheel activity reduces cocaine self-administration in rats; this may, however, require the establishment of compulsive wheel activity. Methods Effects of concurrent wheel activity on intravenous d-methamphetamine (METH) self-administration were examined in male Wistar and Sprague Dawley rats with negligible prior wheel experience. Wistar rats self-administered METH (0.05 mg/kg/inf) under a fixed-ratio 1 (FR1) schedule with concurrent access to an activity wheel during sessions 1–14, 8–21 or 15–21. Control rats which did not self-administer METH had access to an activity wheel during sessions 1–14, 8–21 or 15–28. Sprague Dawley rats self-administered METH (0.1 mg/kg/inf) under FR1 for 14 sessions with either concurrent access to a locked or an unlocked activity wheel. Results METH self-administration was lower when the wheel was available concurrently from the start of self-administration training in both strains, even though Sprague Dawley rats self-administered twice as many METH infusions and ran one-sixth as much on the wheel compared to Wistar rats. Wheel access initiated after 7 or 14 days had no effect on METH self-administration in Wistar rats. Wheel activity was significantly reduced in these groups compared with the group with concurrent wheel and METH access for the first 14 sessions. Conclusions These data show METH self-administration is reduced by exercise if initiated from the start of self-administration and that prior METH self-administration experience interferes with the value of exercise as a reinforcer.

Background There are no approved pharmacotherapies for d-methamphetamine (METH) addiction and existing therapies have limited efficacy. Advances in using immunotherapeutic approaches for cocaine and nicotine addiction have stimulated interest in creating a similar approach for METH addiction. This study investigated whether active vaccination against METH could potentially attenuate responses to METH, in vivo. Methods Male Sprague Dawley rats (N=32) received a 4-boost series with 1 of 3 candidate anti-METH vaccines (MH2(R), MH6, and MH7) or a control keyhole limpet hemocyanin conjugate vaccine (KLH). Effects of METH on rectal temperature and wheel activity at 27°C ambient temperature were determined. The most efficacious vaccine, MH6, was then contrasted with KLH in a subsequent experiment (N=16), wherein radiotelemetry determined home cage locomotor activity and body temperature at 23°C ambient temperature. Results The MH6 vaccine produced high antibody titers with nanomolar affinity for METH and sequestered METH in the periphery of rats. In Experiment 1, the thermoregulatory and psychomotor responses produced by METH at 27°C were blocked in the MH6 group. In Experiment 2, METH-induced decreases in body temperature and locomotor activity at 23°C were also attenuated in the MH6 group. A pharmacokinetic study in Experiment 2 showed that MH6-vaccinated rats had higher METH serum concentrations, yet lower brain METH concentrations than controls, and METH concentrations correlated with individual antibody titer. Conclusions These data demonstrate that active immunopharmacotherapy provides functional protection against physiological and behavioral disruptions induced by METH.

Little is known regarding the abuse liability or the behavioral and physiological effects of MDPV. We present data on the effects of MDPV in rats from both intravenous self‐administration (IVSA) and acute drug challenge experiments. IVSA of MDPV was established on an FR5 schedule to stable intake patterns and high lever discrimination. Dose‐dependent rates of responding were observed under both FR and PR schedules wherein as per‐infusion dose increased, infusions decreased under FR but increased under PR. In acute challenge studies, bolus s.c. injections of MDPV showed a biphasic effect on both body temperature (compared to saline, low doses increased body temperature while high doses decreased body temperature) and activity counts (compared to saline, low doses increased activity while high doses suppressed activity). These initial data indicate that MDPV has an abuse liability that is similar to that of other stimulant drugs of abuse. Additionally, the observed biphasic effects in body temperature and activity may be related to the observed increase in stereotypy at higher doses of MDPV. (Grant DA024105).

At present, there are no approved pharmacotherapies for methamphetamine addiction and existing therapies have limited effect. Recent successes in early clinical trials using immunotherapeutic approaches for cocaine and nicotine addiction have motivated interest in creating similar approaches for methamphetamine (METH) addiction. The current study investigated the effects of a candidate vaccine (MH6) shown to produce METH specific antibodies in mice on METH self‐administration in Sprague Dawley rats. Groups of rats were pretreated with MH6 (n=18) or control vaccine (KLH; n=18) during a 13‐week dosing regimen. This consisted of a priming dose followed by 4 booster doses at 2, 5, 9, and 13 weeks after the prime. Stable, high antibody titers were produced. Subsequently, the effects of vaccination on METH self‐administration were assessed across a range of doses (0.0, 0.01, 0.05, 0.10, 0.15, and 0.25 mg/kg/inf). In general, vaccinated rats self‐administered less METH than non‐vaccinated rats, although different patterns were observed depending on whether the rats were pellet trained prior to initiation of the self‐administration procedure. These data provide evidence that active immunopharmacotherapy can provide functional protection against the behavioral effects of METH.