Selective alpha7-nicotinic agonists normalize inhibition of auditory response in DBA mice.
Abnormal sensory inhibition is a measurable indicator of a sensory processing deficit which is observed in schizophrenia, and other disorders, and which may be heritable. This deficit has also been observed in certain inbred mouse strains where the intensity of the deficit has been correlated with reduction in the number of hippocampal alpha-bungarotoxin-sensitive nicotinic receptors. Nicotine and certain nicotinic agonists produce brief periods of normal sensory inhibition in these mice. Similarly, nicotine also transiently normalizes sensory inhibition in schizophrenics. The present study assessed the effects of a novel nicotinic partial agonist (GTS-21), selective for the alpha-bungarotoxin site, on sensory inhibition in DBA mice, a strain with no sensory inhibition under routine experimental conditions. GTS-21 produced a dose-dependent normalization of sensory inhibition which was blocked by alpha-bungarotoxin but not mecamylamine. In contrast to other nicotinic agonists, normalization of sensory inhibition by GTS-21 and two related anabaseine compounds, DMAB-anabaseine and DMAC-anabaseine, was observed when administered a second time to the animal, after a 40-min delay. Our results indicated that the anabaseine compounds increase sensory inhibition through alpha7 nicotinic receptors, and that their ability to act repeatedly on these receptors may be less affected by desensitization.
Stevens
K E
KE
Medical Research Service, Veterans Affairs Medical Center, Denver, CO 80262, USA. stevensk@sembilan.uchsc.edu
Kem
W R
WR
Mahnir
V M
VM
Freedman
R
R
D000691:Anabasine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001597:Benzylidene Compounds / Q000494:pharmacology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D018722:Nicotinic Agonists / Q000494:pharmacology*; D011619:Psychotropic Drugs / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000502:physiology; D013216:Reflex, Startle / Q000187:drug effects* / Q000502:physiology; D064569:alpha7 Nicotinic Acetylcholine Receptor
C094402:3-(4-dimethylaminobenzylidene)anabaseine; C091714:3-(4-dimethylaminocinnamylidene)anabaseine; D001597:Benzylidene Compounds; C579166:Chrna7 protein, mouse; D018722:Nicotinic Agonists; D011619:Psychotropic Drugs; D011725:Pyridines; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C088936:3-(2,4-dimethoxybenzylidene)anabaseine; D000691:Anabasine