Wheel running tended to attract individuals who are highly motivated to engage in frequent, sustained exercise, which Doxorubicin cell line reflected a voluntary, active physical and mental state, while treadmill running attracts those that are forced to exercise, which reflects an attitude

towards exercise.41 Only very recently have there been studies demonstrating the sex differences in exercise intervention for drug addiction and rehabilitation. In one such study, Sanchez and colleagues42 found that 10-day wheel running after the formation of rat SA attenuated nicotine-seeking in male rats only under the conditions of access to unlocked wheels. However, access to either locked or unlocked wheels was sufficient to suppress nicotine-seeking during extinction in females. Also 14-day wheel running during abstinence on subsequent

cocaine-seeking of rat’s SA can effectively reduce relapse vulnerability in a dose HSP inhibitor dependent manner, and this effect differs by sex and estrous cycle.43 Since females perform wheel and treadmill running differently than males, it is important to include the consideration of sex-specific effectiveness of exercise on drug rehabilitation in animal experiments. In addition to wheel and treadmill running, forced swimming has also been used for studies of exercise rehabilitation. Forced swimming exercises could be evaluated for exercise performance, psychological status (anxiety and stress), cognition (learning and memory), etc. 44 and 45 It also showed the same effectiveness as displayed in voluntary wheel running in alcohol conditioned place aversion (CPA), 46 and 47 suggesting that forced swimming may be one mode for exercise intervention for drug addiction. Again, compared to male rats, female rats were more active in water 48 and swam faster in speed with less sign of fatigue. 49 and 50 Exercises attenuate drug-seeking behaviors during drug initiation, escalation, extinction, abstinence, and relapse.51 and 52 It is crucial to decrease the susceptibility (preventive effect) at an early stage of drug addiction and reduce the

drug craving (therapeutic effect) at later stages in order to prevent relapse. Montelukast Sodium As most of animal studies in biology research show, researches about exercise as a means of prevention on drug abuse are limited by investigating male animals only,53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67 and 68 with a few studies on female animals,69, 70, 71, 72, 73 and 74 while the others did not specify the gender.75 and 76 In regard to the sex differences as shown in Table 1, the results of these studies have been inconsistent. One study found that chronic forced treadmill exercise for 6 weeks induced reduction of drug craving behavior in adolescent female and male rats, but only male rats showed inhibited CPP.