Tolerance can occur with repeated drug administration. The development of tolerance to the hedonic effects of drugs may favor escalation of drug consumption and development of addiction.46 Instead of hyperlocomotion, acute cannabinoid treatment produces hypolocomotion in rodents. Pretreatment with systemic SL327 does not prevent the development of hypolocomotion induced by acute THC injections. Such pretreatments do prevent the development of tolerance to the hypolocomotor effects of repeated THC injection in mice.25 In summary, ERK activity appears to be important for the expression of hyperlocomotor activity from acute administration of many addictive drugs, the development of psychomotor sensitization to psychostimulants, and the development of tolerance to the hypolocomotor effects of cannabinoids.
