Haloperidol modulates noradrenergic responses to aversive stimulation depending on treatment duration

Antipsychotic drugs are widely used in the treatment of schizophrenia. While their effects are considered to be due to a modulation of dopaminergic and serotonergic signaling, little is known about their effects on noradrenergic (NA) activity in the brain. In this study, rats received either a 6 d or 14 d treatment with haloperidol using osmotic minipumps. Noradrenaline responses to novelty, appetitive food and to an aversive tail pinch were measured in the prefrontal cortex, nucleus accumbens and caudate putamen (CPu) using in vivo microdialysis. Haloperidol significantly decreased baseline NA levels after short and long term treatment. A tail pinch significantly increased NA activity in the CPu. This effect was attenuated by haloperidol in a treatment duration-dependent way. This study suggests that haloperidol modulates NA baseline activity and reduces NA responses to mildly aversive stimuli depending on treatment duration.