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Effects of the T-type calcium channel antagonist Z944 on paired associates learning and locomotor activity in rats treated with the NMDA receptor antagonist MK-801.
- Source :
-
Psychopharmacology [Psychopharmacology (Berl)] 2018 Nov; Vol. 235 (11), pp. 3339-3350. Date of Electronic Publication: 2018 Sep 24. - Publication Year :
- 2018
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Abstract
- Rationale: Currently available antipsychotics are unsatisfactory given their side effects and limited efficacy for the cognitive symptoms of schizophrenia. Many currently available drugs, such as haloperidol, are T-type calcium channel antagonists in addition to their well-established antagonism of dopamine D2 receptors. Thus, preclinical research into the effects of T-type calcium channel antagonists/blockers in behavioral assays related to schizophrenia may inform novel therapeutic strategies.<br />Objectives: We explored the effects of a recently developed highly selective T-type calcium channel antagonist, Z944 (2.5, 5.0, 10.0 mg/kg), on the MK-801 (0.15 mg/kg) model of acute psychosis.<br />Methods: To examine the effects of Z944 on behaviors relevant to schizophrenia, we tested touchscreen-based paired associates learning given its relevance to the cognitive symptoms of the disorder and locomotor activity given its relevance to the positive symptoms.<br />Results: Acute treatment with Z944 failed to reverse the visuospatial associative memory impairments caused by MK-801 in paired associates learning. The highest dose of drug (10.0 mg/kg) given alone produced subtle impairments on paired associates learning. In contrast, Z944 (5.0 mg/kg) blocked the expected increase in locomotion following MK-801 treatment in a locomotor assay.<br />Conclusions: These experiments provide support that Z944 may reduce behaviors relevant to positive symptoms of schizophrenia, although additional study of its effects on cognition is required. These findings and other research suggest T-type calcium channel antagonists may be an alternative to currently available antipsychotics with less serious side effects.
- Subjects :
- Acetamides therapeutic use
Animals
Association Learning physiology
Benzamides therapeutic use
Calcium Channel Blockers therapeutic use
Calcium Channels, T-Type physiology
Conditioning, Operant drug effects
Conditioning, Operant physiology
Dose-Response Relationship, Drug
Excitatory Amino Acid Antagonists toxicity
Locomotion physiology
Male
Memory Disorders chemically induced
Memory Disorders drug therapy
Piperidines
Rats
Rats, Long-Evans
Schizophrenia chemically induced
Schizophrenia drug therapy
Acetamides pharmacology
Association Learning drug effects
Benzamides pharmacology
Calcium Channel Blockers pharmacology
Dizocilpine Maleate toxicity
Locomotion drug effects
Receptors, N-Methyl-D-Aspartate antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 1432-2072
- Volume :
- 235
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Psychopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 30251162
- Full Text :
- https://doi.org/10.1007/s00213-018-5040-3