Haloperidol Administration in Humans Lowers Plasma Nerve Growth Factor Level: Evidence that Sedation Induces Opposite Effects to Arousal

Abstract

Studies reported in recent years have indicated that the level of nerve growth factor (NGF), in both the brain and in the bloodstream, increases following stressful events and anxiety-associated behaviour. These observations prompted us to investigate whether an anti-arousal drug would induce an opposite effect. We have reported that the administration of haloperidol (HA), a neuroleptic drug clinically used for psychiatric disorders, decreases NGF levels in the hypothalamus of adult male mice. In the present study, we showed that HA reduced the basal NGF plasma levels in 8 neuroleptic-free schizophrenic patients. These observations strengthen the hypothesis that NGF may play a functional role in stress-coping responses.

Antipsychotic Drugs: Comparison in Animal Models of Efficacy, Neurotransmitter Regulation, and Neuroprotection

“…Another study reported that serum BDNF levels in patients treated with clozapine were not significantly higher than values from patients treated with typical antipsychotics (Grillo et al, 2007), although serum BDNF levels were strongly and positively correlated with the dose of clozapine (Grillo et al, 2007). These findings are consistent with an earlier study reporting reductions in basal NGF levels in neuroleptic-free patients with schizophrenia subsequently treated with haloperidol (Aloe et al, 1997). Other studies, though, have not shown increases in neurotrophin levels after treatment with SGAs (Pirildar et al, 2004; Tan et al, 2005).…”

Modulation of nerve growth factor and choline acetyltransferase expression in rat hippocampus after chronic exposure to haloperidol, risperidone, and olanzapine

“…Reduced cholinergic activity in post-mortem brain has been reported to correlate with pre-mortem cognitive performance in schizophrenics (Powchik et al 1998). Lower plasma NGF levels were reported in neuroleptic free schizophrenic patients (Bersani et al 1999) as well as in HAL-treated chronic schizophrenic patients (Aloe et al 1997). Recently, we reported that plasma NGF levels were significantly lower in never-medicated first-episode psychotic patients compared with those of normal agematched controls.…”

The expanding role of nerve growth factor: from neurotrophic activity to immunologic diseases

“…Of particular interest also is the observation that the level of NGF is enhanced in the nervous, endocrine, and immune systems in response to psychologic stress (19,(136)(137)(138), leading to the hypothesis that NGF is implicated in homeostatic responses (6). Recent observations in both rodents and in man, demonstrating that drugs which interfere with arousal behavior lower basal NGF, seem to support this hypothesis.…”