Development of selective tolerance to the serotonin behavioral syndrome and suppression of locomotor activity after repeated administration of either 5-MeODMT or mCPP.

Repeated administration of a drug that activates 5-HT1A receptors in rats leads to tolerance to the behavioral effects of that same drug, but not to the effects of a drug that activates 5-HT1B receptors. Conversely, repeated administration of the 5-HT1B-activating drug produces tolerance to its own effects but not to those of the 5-HT1A-activating drug. This lack of cross-tolerance suggests that different serotonin receptor subtypes (5-HT1A and 5-HT1B) mediate different behaviors: the serotonin behavioral syndrome and suppression of locomotor activity.

Study at a glance

Abstract

Repeated administration to rats of the 5-HT1A-selective agonist 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) produced tolerance to the ability of a test dose of 5-MeODMT to produce the serotonin behavioral syndrome, but not to the ability of a test dose of the 5-HT1B-selective agonist m-chlorophenylpiperazine (mCPP) to decrease locomotor activity. Conversely, repeated administration of mCPP produced tolerance to the ability of a test dose of mCPP to decrease locomotor activity, but not to the ability of a test dose of 5-MeODMT to elicit the serotonin behavioral syndrome. The lack of cross-tolerance between these two selective agonists is consistent with the idea that the serotonin behavioral syndrome and suppression of locomotor activity are mediated by different subtypes of the 5-HT1 receptor.