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Differential effects of d- and l-enantiomers of govadine on distinct forms of cognitive flexibility and a comparison with dopaminergic drugs.
- Source :
-
Psychopharmacology . Apr2021, Vol. 238 Issue 4, p1069-1085. 17p. 2 Charts, 4 Graphs. - Publication Year :
- 2021
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Abstract
- Rationale: There is an urgent need for novel drugs for treating cognitive deficits that are defining features of schizophrenia. The individual d- and l-enantiomers of the tetrahydroprotoberberine (THPB) d,l-govadine have been proposed for the treatment of cognitive deficiencies and positive symptoms of schizophrenia, respectively. Objectives: We examined the effects of d-, l-, or d,l-govadine on two distinct forms of cognitive flexibility perturbed in schizophrenia and compared them to those induced by a selective D1 receptor agonist and D2 receptor antagonist. Methods: Male rats received d-, l-, or d,l-govadine (0.3, 0.5, and 1.0 mg/kg), D1 agonist SKF81297(0.1, 0.3, and 1.0 mg/kg), or D2 antagonist haloperidol (0.1–0.2 mg/kg). Experiment 1 used a strategy set-shifting task (between-subjects). In experiment 2, well-trained rats were tested on a probabilistic reversal task (within-subjects). Results: d-Govadine improved set-shifting across all doses, whereas higher doses of l-govadine impaired set-shifting. SKF81297 reduced perseverative errors at the lowest dose. Low/high doses of haloperidol increased/decreased set-shifting errors, the latter "improvement" attributable to impaired retrieval of a previous acquired rule. Probabilistic reversal performance was less affected by these drugs, but d-govadine reduced errors during the first reversal, whereas l-govadine impaired initial discrimination learning. d,l-Govadine had no reliable cognitive effects but caused psychomotor slowing like l-govadine and haloperidol. Conclusions: These findings further highlight differences between two enantiomers of d,l-govadine that may reflect differential modulation of D1 and D2 receptors. These preclinical findings give further impetus to formal clinical evaluation of d-govadine as a treatment for cognitive deficiencies related to schizophrenia. [ABSTRACT FROM AUTHOR]
- Subjects :
- *DOPAMINE agents
*COGNITIVE flexibility
*DOPAMINE agonists
*SYMPTOMS
*HALOPERIDOL
Subjects
Details
- Language :
- English
- ISSN :
- 00333158
- Volume :
- 238
- Issue :
- 4
- Database :
- Academic Search Index
- Journal :
- Psychopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 149336176
- Full Text :
- https://doi.org/10.1007/s00213-020-05754-y