Paradoxical constitutive behavioral sensitization to amphetamine in mice lacking 5-HT2A receptors

Rationale Although locomotor response to d-amphetamine is considered as mediated by an increased release of dopamine in the ventral striatum, blockade of either α1b-adrenergic or 5-HT2A receptors almost completely inhibits d-amphetamine-induced locomotor response in mice. In agreement with this finding, mice lacking α1b-adrenergic receptors hardly respond to d-amphetamine. However, we show here that, paradoxically, mice lacking 5-HT2A receptors (5-HT2A-R KO) exhibit a twofold higher locomotor response to d-amphetamine than wild-type (WT) littermates.