serotonergic neurotransmission in the ventral hippocampus is enhanced by corticosterone and altered by chronic amphetamine treatment the ventral hippocampus modulates anxietylike behavior in rats and serotonergic transmission within the hippocampus facilitates adaptation to stress chronic amphetamine treatment results in anxietylike behavior in rats and reduced monoamine concentrations in the ventral hippocampus since reduced hippocampal serotonergic transmission in response to stress is observed in rats that display high anxietylike behavior anxiety states in amphetaminetreated rats may be associated with reduced stressrelated serotonergic transmission in the hippocampus therefore using in vivo microdialysis in anesthetized rats we investigated the effect of corticosterone infused locally into the ventral hippocampus on serotonergic transmission and the effect of chronic amphetamine pretreatment on corticosteroid receptor protein expression and the corticosteroneinduced serotonergic response extracellular serotonin in the ventral hippocampus was increased by corticosterone in drug naive rats and this corticosteroneinduced serotonin augmentation was blocked by the glucocorticoid receptor antagonist mifepristone furthermore chronic pretreatment with amphetamine abolished the serotonin response to physiologically relevant corticosterone levels and reduced glucocorticoid receptor protein expression together our results suggest that chronic amphetamine exposure reduces serotonergic neurotransmission in part via alterations to glucocorticoid receptorfacilitation of serotonin release in the rat ventral hippocampus reduced serotonergic activity in the ventral hippocampus may contribute to altered stress responses and adaptive coping following repeated drug exposure