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Habituation of acoustic startle is disrupted by psychotomimetic drugs: differential dependence on dopaminergic and nitric oxide modulatory mechanisms.
Psychopharmacology (Berl). 2004 Nov; 176(3-4):440-50.P

Abstract

RATIONALE

A deficit in attention and information processing has been considered a central feature in schizophrenia, which might lead to stimulus overload and cognitive fragmentation. It has been shown that patients with schizophrenia display a relative inability to gate incoming stimuli. Thus, patients repeatedly subjected to acoustic startle-eliciting stimuli habituate less to these stimuli than controls. Furthermore, schizophrenia-like symptoms can be induced by pharmacological manipulations in humans by psychotomimetic drugs, e.g. phencyclidine (PCP) and D-amphetamine (D-AMP). Recent studies show that the behavioural and biochemical effects of PCP in rodents are blocked by nitric oxide synthase (NOS) inhibitors, suggesting that NO plays an important role in at least the pharmacological effects of PCP.

OBJECTIVES

The first aim of the present study was to investigate if PCP, MK-801 and D-AMP impair habituation of acoustic startle in mice. Secondly, we examine the effect of the NOS inhibitor, L-NAME, and the dopamine receptor antagonist, haloperidol, on drug-induced deficit in habituation.

RESULTS

PCP (4 mg/kg), MK-801 (0.4 mg/kg) and D-AMP (5.0 mg/kg), impaired habituation of the acoustic startle response in mice. This effect was reversed by the NOS inhibitor, L-NAME. The typical antipsychotic, haloperidol, reversed the effects of PCP and D-AMP, but not that of MK-801.

CONCLUSIONS

The finding that PCP, MK-801 and D-AMP impair habituation in mice is consistent with the idea that these treatments model certain filter deficits seen in schizophrenic patients. Furthermore, the present results suggest that NO is critically involved in these effects on habituation, whereas that of dopamine is less clear.

Authors+Show Affiliations

Department of Pharmacology, The Sahlgrenska Academy, Göteborg University, PO Box 431, 405-30, Goteborg, Sweden.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15173930

Citation

Klamer, Daniel, et al. "Habituation of Acoustic Startle Is Disrupted By Psychotomimetic Drugs: Differential Dependence On Dopaminergic and Nitric Oxide Modulatory Mechanisms." Psychopharmacology, vol. 176, no. 3-4, 2004, pp. 440-50.
Klamer D, Pålsson E, Revesz A, et al. Habituation of acoustic startle is disrupted by psychotomimetic drugs: differential dependence on dopaminergic and nitric oxide modulatory mechanisms. Psychopharmacology (Berl). 2004;176(3-4):440-50.
Klamer, D., Pålsson, E., Revesz, A., Engel, J. A., & Svensson, L. (2004). Habituation of acoustic startle is disrupted by psychotomimetic drugs: differential dependence on dopaminergic and nitric oxide modulatory mechanisms. Psychopharmacology, 176(3-4), 440-50.
Klamer D, et al. Habituation of Acoustic Startle Is Disrupted By Psychotomimetic Drugs: Differential Dependence On Dopaminergic and Nitric Oxide Modulatory Mechanisms. Psychopharmacology (Berl). 2004;176(3-4):440-50. PubMed PMID: 15173930.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Habituation of acoustic startle is disrupted by psychotomimetic drugs: differential dependence on dopaminergic and nitric oxide modulatory mechanisms. AU - Klamer,Daniel, AU - Pålsson,Erik, AU - Revesz,Aron, AU - Engel,Jörgen A, AU - Svensson,Lennart, Y1 - 2004/06/02/ PY - 2004/02/04/received PY - 2004/03/29/accepted PY - 2004/6/3/pubmed PY - 2005/3/2/medline PY - 2004/6/3/entrez SP - 440 EP - 50 JF - Psychopharmacology JO - Psychopharmacology (Berl) VL - 176 IS - 3-4 N2 - RATIONALE: A deficit in attention and information processing has been considered a central feature in schizophrenia, which might lead to stimulus overload and cognitive fragmentation. It has been shown that patients with schizophrenia display a relative inability to gate incoming stimuli. Thus, patients repeatedly subjected to acoustic startle-eliciting stimuli habituate less to these stimuli than controls. Furthermore, schizophrenia-like symptoms can be induced by pharmacological manipulations in humans by psychotomimetic drugs, e.g. phencyclidine (PCP) and D-amphetamine (D-AMP). Recent studies show that the behavioural and biochemical effects of PCP in rodents are blocked by nitric oxide synthase (NOS) inhibitors, suggesting that NO plays an important role in at least the pharmacological effects of PCP. OBJECTIVES: The first aim of the present study was to investigate if PCP, MK-801 and D-AMP impair habituation of acoustic startle in mice. Secondly, we examine the effect of the NOS inhibitor, L-NAME, and the dopamine receptor antagonist, haloperidol, on drug-induced deficit in habituation. RESULTS: PCP (4 mg/kg), MK-801 (0.4 mg/kg) and D-AMP (5.0 mg/kg), impaired habituation of the acoustic startle response in mice. This effect was reversed by the NOS inhibitor, L-NAME. The typical antipsychotic, haloperidol, reversed the effects of PCP and D-AMP, but not that of MK-801. CONCLUSIONS: The finding that PCP, MK-801 and D-AMP impair habituation in mice is consistent with the idea that these treatments model certain filter deficits seen in schizophrenic patients. Furthermore, the present results suggest that NO is critically involved in these effects on habituation, whereas that of dopamine is less clear. SN - 0033-3158 UR - https://www.unboundmedicine.com/medline/citation/15173930/Habituation_of_acoustic_startle_is_disrupted_by_psychotomimetic_drugs:_differential_dependence_on_dopaminergic_and_nitric_oxide_modulatory_mechanisms_ L2 - https://dx.doi.org/10.1007/s00213-004-1901-z DB - PRIME DP - Unbound Medicine ER -