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
© 2017, Springer-Verlag Berlin Heidelberg. Rationale: 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,...
| Main Authors: | , , , |
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| Format: | Journal Article |
| Language: | English |
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2017
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| Online Access: | http://hdl.handle.net/20.500.11937/81122 |
| _version_ | 1848764320144424960 |
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| author | Lins, Brittney Marks, W.N. Phillips, A.G. Howland, J.G. |
| author_facet | Lins, Brittney Marks, W.N. Phillips, A.G. Howland, J.G. |
| author_sort | Lins, Brittney |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | © 2017, Springer-Verlag Berlin Heidelberg. Rationale: 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. Objectives: 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. Methods: 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. Results: 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. Conclusions: 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. |
| first_indexed | 2025-11-14T11:17:29Z |
| format | Journal Article |
| id | curtin-20.500.11937-81122 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| language | eng |
| last_indexed | 2025-11-14T11:17:29Z |
| publishDate | 2017 |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-811222021-01-15T06:58:29Z 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 Lins, Brittney Marks, W.N. Phillips, A.G. Howland, J.G. Antipsychotic Dopamine Schizophrenia Animals Antipsychotic Agents Apomorphine Berberine Alkaloids Dizocilpine Maleate Dopamine Agonists Dose-Response Relationship, Drug Excitatory Amino Acid Antagonists Male Prepulse Inhibition Rats Rats, Long-Evans Receptors, Dopamine D2 Reflex, Startle Schizophrenia Stereoisomerism © 2017, Springer-Verlag Berlin Heidelberg. Rationale: 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. Objectives: 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. Methods: 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. Results: 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. Conclusions: 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. 2017 Journal Article http://hdl.handle.net/20.500.11937/81122 10.1007/s00213-017-4540-x eng restricted |
| spellingShingle | Antipsychotic Dopamine Schizophrenia Animals Antipsychotic Agents Apomorphine Berberine Alkaloids Dizocilpine Maleate Dopamine Agonists Dose-Response Relationship, Drug Excitatory Amino Acid Antagonists Male Prepulse Inhibition Rats Rats, Long-Evans Receptors, Dopamine D2 Reflex, Startle Schizophrenia Stereoisomerism Lins, Brittney Marks, W.N. Phillips, A.G. Howland, J.G. 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 |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | Antipsychotic Dopamine Schizophrenia Animals Antipsychotic Agents Apomorphine Berberine Alkaloids Dizocilpine Maleate Dopamine Agonists Dose-Response Relationship, Drug Excitatory Amino Acid Antagonists Male Prepulse Inhibition Rats Rats, Long-Evans Receptors, Dopamine D2 Reflex, Startle Schizophrenia Stereoisomerism |
| url | http://hdl.handle.net/20.500.11937/81122 |