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Dissociable effects of the d- and l- enantiomers of govadine on the disruption of prepulse inhibition by MK-801 and apomorphine in male Long-Evans rats

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Dissociable effects of the d- and l- enantiomers of govadine on the disruption of prepulse inhibition by MK-801 and apomorphine in male Long-Evans rats

Content Provider	Springer Nature Link
Author	Lins, Brittney R. Marks, Wendie N. Phillips, Anthony G. Howland, John G.
Copyright Year	2017
Abstract	The search for novel antipsychotic drugs to treat schizophrenia is driven by the poor treatment efficacy, serious side effects, and poor patient compliance of current medications. Recently, a class of compounds known as tetrahydroprotoberberines, which includes the compound d,l-govadine, have shown promise in preclinical rodent tests relevant to schizophrenia. To date, the effect of govadine on prepulse inhibition (PPI), a test for sensorimotor gating commonly used to assess the effects of putative treatments for schizophrenia, has not been determined.The objective of the present study was to determine the effects of each enantiomer of govadine (d- and l-govadine) on PPI alone and its disruption by the distinct pharmacological compounds apomorphine and MK-801.Male Long-Evans rats were treated systemically with d- or l-govadine and apomorphine or MK-801 prior to PPI. The PPI paradigm employed here included parametric manipulations of the prepulse intensity and the interval between the prepulse and pulse.Acute MK-801 (0.15 mg/kg) significantly increased the startle response to startle pulses alone, while both MK-801 and apomorphine (0.2 mg/kg) significantly increased reactivity to prepulse-alone trials. Both MK-801 and apomorphine disrupted PPI. In addition, d-govadine alone significantly disrupted PPI in the apomorphine experiment. Pretreatment with l-, but not d-, govadine (1.0 mg/kg) blocked the effect of apomorphine and MK-801 on PPI. Treatment of rats with l-govadine alone (0.3, 1.0, 3.0 mg/kg) also dose-dependently increased PPI.Given the high affinity of l-govadine for dopamine D2 receptors, these results suggest that further testing of l-govadine as an antipsychotic is warranted.
Starting Page	1079
Ending Page	1091
Page Count	13
File Format	PDF
ISSN	00333158
Journal	Psychopharmacology
Volume Number	234
Issue Number	7
e-ISSN	14322072
Language	English
Publisher	Springer Berlin Heidelberg
Publisher Date	2017-02-08
Publisher Place	Berlin, Heidelberg
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Dopamine Antipsychotic Schizophrenia Neurosciences Pharmacology/Toxicology Psychiatry
Content Type	Text
Resource Type	Article
Subject	Pharmacology

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