Calcium antagonists in the olfactory bulbectomy animal model of depression: effect on the cortical NMDA receptor complex.
Voltage-dependent calcium channel (VDCC) antagonists are active in the forced swim test and in learned helplessness behavioral paradigms, suggesting their antidepressant efficacy. In fact, some clinical reports show that VDCC antagonists are useful in a treatment of affective disorders. Because none of the VDCC antagonists has been tested in the olfactory bulbectomy (OB) model of depression, we examined the efficacy of chronic treatment with verapamil and diltiazem to reduce OB-induced hyperactivity. We also observed the effect of these treatments on OB-induced alterations in the NMDA receptor complex in rat cortex. We report that chronic administration of verapamil (20 mg/kg) and diltiazem (10 mg/kg) did not reduced OB-induced hyperactivity, although these drugs reduced the potency of glycine to inhibit [3H]5,7-dichlorokynurenic acid (DCKA) binding to strychnine-insensitive glycine sites of the NMDA receptor complex. OB also reduced the potency of glycine to inhibit [3H]5,7-DCKA binding, and this reduction was slightly attenuated by chronic treatment with both drugs. These data indicate that: 1) verapamil and diltiazem are not effective in OB model of depression, 2) VDCC antagonists'-induced effect in the glycine sites of the NMDA receptor complex is not species-specific, and 3) there is no direct relationship between OB-induced hyperactivity and alterations in strychnine-insensitive glycine sites of the NMDA receptor complex.
Nowak
G
G
Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson 39216-4505, USA.
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003863:Depression / Q000188:drug therapy / Q000503:physiopathology*; D004110:Diltiazem / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000378:metabolism; D005998:Glycine / Q000031:analogs & derivatives; D007736:Kynurenic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009830:Olfactory Bulb / Q000502:physiology*; D011485:Protein Binding / Q000187:drug effects; D011849:Radioactive Tracers; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects* / Q000502:physiology; D014316:Tritium; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D018691:Excitatory Amino Acid Antagonists; D011849:Radioactive Tracers; D016194:Receptors, N-Methyl-D-Aspartate; D014316:Tritium; D014700:Verapamil; D004110:Diltiazem; D007736:Kynurenic Acid; C066192:5,7-dichlorokynurenic acid; D005998:Glycine