Time-dependent effects of haloperidol and ziprasidone on nerve growth factor, cholinergic neurons, and spatial learning in rats

Alvin V. Terry, Vinay Parikh, Debra A. Gearhart, Anilkumar Pillai, Elizabeth Hohnadel, Samantha Warner, Henry A. Nasrallah, Sahebarao P. Mahadik

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

In this rodent study, we evaluated the effects of different time periods (7, 14, 45, and 90 days) of oral treatment with haloperidol (HAL; 2.0 mg/kg/day) or ziprasidone (ZIP; 12.0 mg/kg/day) on nerve growth factor (NGF) and choline acetyltransferase (ChAT) levels in the hippocampus, and we subsequently assessed water maze task performance, prepulse inhibition (PPI) of the auditory gating response, and several NGF-related proteins and cholinergic markers after 90 days of treatment. Seven and 14 days of treatment with either HAL or ZIP resulted in a notable increase in NGF and ChAT immunoreactivity in the dentate gyrus (DG), CA1, and CA3 areas of the hippocampus. After 45 days, NGF and ChAT immunoreactivity had abated to control levels in ZIP-treated animals, but it was markedly reduced in HAL-treated subjects. After 90 days of treatment, NGF and ChAT levels were substantially lower than controls in both antipsychotic groups. Furthermore, after 90 days of treatment and a drug-free washout period, water maze performance (but not PPI) was impaired in both antipsychotic groups, although the decrement was greater in the HAL group. Several NGF-related and cholinergic proteins were diminished in the brains of subjects treated with either neuroleptic as well. These data support the premise that, although ZIP (given chronically) seems somewhat superior to HAL due to less pronounced behavioral effects and a more delayed appearance of neurochemical deficits, both antipsychotics produce time-dependent deleterious effects on NGF, cholinergic markers (i.e., important neurobiological substrates of memory), and cognitive function.

Original languageEnglish (US)
Pages (from-to)709-724
Number of pages16
JournalJournal of Pharmacology and Experimental Therapeutics
Volume318
Issue number2
DOIs
StatePublished - Jul 20 2006

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Cholinergic Neurons
Nerve Growth Factor
Haloperidol
Choline O-Acetyltransferase
Antipsychotic Agents
Cholinergic Agents
Hippocampus
Water
Dentate Gyrus
Task Performance and Analysis
ziprasidone
Spatial Learning
Cognition
Rodentia
Proteins
Brain
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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Time-dependent effects of haloperidol and ziprasidone on nerve growth factor, cholinergic neurons, and spatial learning in rats. / Terry, Alvin V.; Parikh, Vinay; Gearhart, Debra A.; Pillai, Anilkumar; Hohnadel, Elizabeth; Warner, Samantha; Nasrallah, Henry A.; Mahadik, Sahebarao P.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 318, No. 2, 20.07.2006, p. 709-724.

Research output: Contribution to journalArticle

Terry, Alvin V. ; Parikh, Vinay ; Gearhart, Debra A. ; Pillai, Anilkumar ; Hohnadel, Elizabeth ; Warner, Samantha ; Nasrallah, Henry A. ; Mahadik, Sahebarao P. / Time-dependent effects of haloperidol and ziprasidone on nerve growth factor, cholinergic neurons, and spatial learning in rats. In: Journal of Pharmacology and Experimental Therapeutics. 2006 ; Vol. 318, No. 2. pp. 709-724.
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