Effects of D- and L-govadine on the disruption of touchscreen object-location paired associates learning in rats by acute MK-801 treatment
© 2015 Springer-Verlag Berlin Heidelberg. Rationale: New pharmacological treatments for the cognitive deficits in schizophrenia are needed. Tetrahydroprotoberberines, such as govadine, are one class of compounds with dopaminergic activities that may be useful in treating some aspects of the cognitiv...
| Main Authors: | , , |
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| Format: | Journal Article |
| Language: | English |
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2015
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| Online Access: | http://hdl.handle.net/20.500.11937/81125 |
| _version_ | 1848764320945537024 |
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| author | Lins, Brittney Phillips, A.G. Howland, J.G. |
| author_facet | Lins, Brittney Phillips, A.G. Howland, J.G. |
| author_sort | Lins, Brittney |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | © 2015 Springer-Verlag Berlin Heidelberg. Rationale: New pharmacological treatments for the cognitive deficits in schizophrenia are needed. Tetrahydroprotoberberines, such as govadine, are one class of compounds with dopaminergic activities that may be useful in treating some aspects of the cognitive symptoms of the disorder. Objective: The objective of the present studies was to test the effects of the d- and l-enantiomers of govadine on the impairment in a paired-associate learning (PAL) task produced by acute MK-801 in rats. We also assessed effects of the typical antipsychotic haloperidol as a comparator compound. Methods: MK-801 (0.05, 0.1, 0.15, and 0.2 mg/kg), d- and l-govadine (0.3, 1.0, and 3.0 mg/kg), and haloperidol (0.05, 0.1, and 0.25 mg/kg) were administered acutely to rats well trained on the PAL task in touchscreen-equipped operant conditioning chambers. Results: Acute MK-801 impaired performance of PAL in a dose-dependent manner by reducing accuracy and increasing correction trials. l-Govadine (1.0 mg/kg), but not d-govadine, blocked the disruptive effects of MK-801 (0.15 mg/kg) on PAL. Haloperidol failed to affect the MK-801-induced disruption of PAL. Higher doses of l-govadine and haloperidol dramatically impaired performance of the task which confounded interpretation of cognitive outcomes. Conclusion: l-Govadine appears unique in its ability to improve performance of the MK-801-induced impairment in the PAL task. This behavioral effect may relate the ability of l-govadine to antagonize dopamine D2 receptors while also promoting dopamine efflux. Future research should further characterize the role of the dopamine system in the rodent PAL task to elucidate the mechanisms of its pro-cognitive effects. |
| first_indexed | 2025-11-14T11:17:29Z |
| format | Journal Article |
| id | curtin-20.500.11937-81125 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| language | eng |
| last_indexed | 2025-11-14T11:17:29Z |
| publishDate | 2015 |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-811252021-01-15T06:58:29Z Effects of D- and L-govadine on the disruption of touchscreen object-location paired associates learning in rats by acute MK-801 treatment Lins, Brittney Phillips, A.G. Howland, J.G. Antipsychotic Cognition Dopamine receptor Haloperidol NMDA receptor Schizophrenia Animals Antipsychotic Agents Berberine Alkaloids Conditioning, Operant Dizocilpine Maleate Dose-Response Relationship, Drug Male Paired-Associate Learning Photic Stimulation Rats Rats, Long-Evans Receptors, Dopamine D2 Schizophrenia © 2015 Springer-Verlag Berlin Heidelberg. Rationale: New pharmacological treatments for the cognitive deficits in schizophrenia are needed. Tetrahydroprotoberberines, such as govadine, are one class of compounds with dopaminergic activities that may be useful in treating some aspects of the cognitive symptoms of the disorder. Objective: The objective of the present studies was to test the effects of the d- and l-enantiomers of govadine on the impairment in a paired-associate learning (PAL) task produced by acute MK-801 in rats. We also assessed effects of the typical antipsychotic haloperidol as a comparator compound. Methods: MK-801 (0.05, 0.1, 0.15, and 0.2 mg/kg), d- and l-govadine (0.3, 1.0, and 3.0 mg/kg), and haloperidol (0.05, 0.1, and 0.25 mg/kg) were administered acutely to rats well trained on the PAL task in touchscreen-equipped operant conditioning chambers. Results: Acute MK-801 impaired performance of PAL in a dose-dependent manner by reducing accuracy and increasing correction trials. l-Govadine (1.0 mg/kg), but not d-govadine, blocked the disruptive effects of MK-801 (0.15 mg/kg) on PAL. Haloperidol failed to affect the MK-801-induced disruption of PAL. Higher doses of l-govadine and haloperidol dramatically impaired performance of the task which confounded interpretation of cognitive outcomes. Conclusion: l-Govadine appears unique in its ability to improve performance of the MK-801-induced impairment in the PAL task. This behavioral effect may relate the ability of l-govadine to antagonize dopamine D2 receptors while also promoting dopamine efflux. Future research should further characterize the role of the dopamine system in the rodent PAL task to elucidate the mechanisms of its pro-cognitive effects. 2015 Journal Article http://hdl.handle.net/20.500.11937/81125 10.1007/s00213-015-4064-1 eng restricted |
| spellingShingle | Antipsychotic Cognition Dopamine receptor Haloperidol NMDA receptor Schizophrenia Animals Antipsychotic Agents Berberine Alkaloids Conditioning, Operant Dizocilpine Maleate Dose-Response Relationship, Drug Male Paired-Associate Learning Photic Stimulation Rats Rats, Long-Evans Receptors, Dopamine D2 Schizophrenia Lins, Brittney Phillips, A.G. Howland, J.G. Effects of D- and L-govadine on the disruption of touchscreen object-location paired associates learning in rats by acute MK-801 treatment |
| title | Effects of D- and L-govadine on the disruption of touchscreen object-location paired associates learning in rats by acute MK-801 treatment |
| title_full | Effects of D- and L-govadine on the disruption of touchscreen object-location paired associates learning in rats by acute MK-801 treatment |
| title_fullStr | Effects of D- and L-govadine on the disruption of touchscreen object-location paired associates learning in rats by acute MK-801 treatment |
| title_full_unstemmed | Effects of D- and L-govadine on the disruption of touchscreen object-location paired associates learning in rats by acute MK-801 treatment |
| title_short | Effects of D- and L-govadine on the disruption of touchscreen object-location paired associates learning in rats by acute MK-801 treatment |
| title_sort | effects of d- and l-govadine on the disruption of touchscreen object-location paired associates learning in rats by acute mk-801 treatment |
| topic | Antipsychotic Cognition Dopamine receptor Haloperidol NMDA receptor Schizophrenia Animals Antipsychotic Agents Berberine Alkaloids Conditioning, Operant Dizocilpine Maleate Dose-Response Relationship, Drug Male Paired-Associate Learning Photic Stimulation Rats Rats, Long-Evans Receptors, Dopamine D2 Schizophrenia |
| url | http://hdl.handle.net/20.500.11937/81125 |