Influence of inflammatory nociception on the anxiolytic-like effect of diazepam and buspirone in rats.
BACKGROUND
The effect of anxiety on nociception has been evaluated but not that of nociception on anxiety.


OBJECTIVE
The study was conducted to analyse the influence of nociception on basal levels of anxiety-like behaviour and on the action of anxiolytic drugs.


METHODS
Nociception was induced by an intra-articular injection of uric acid at 3.75 or 7.5%. Experimental anxiety was determined in the rat burying behaviour and the elevated plus maze tests. To separate specific anxiety-related drug actions, a spontaneous ambulatory test was included. The anxiolytics, buspirone (2.5 and 5.0 mg/kg, i.p.) and diazepam (0.5, 1.0 and 2.0 mg/kg, i.p.), were used.


RESULTS
In the nociception test, the pain-induced functional impairment rat model, uric acid at 3.75 and 7.5% had an effect of around 35 and 75%, respectively. Uric acid (UA) at the lower dose (3.75%) lacked an effect on burying behaviour but significantly increased the time spent and number of entries to the open arms; the higher UA dose (7.5%) produced a significant increase in the time spent and number of entries to the open arms and a statistically significant reduction in cumulative burying. Diazepam and buspirone produced a clear dose-dependent reduction in cumulative burying. In the plus maze, diazepam also induced an increase in the time spent and number of entries to the open arms. In the burying behaviour test, rats with a mild level of nociception (uric acid at 7.5%) were insensitive to the anxiolytic-like effect of these anxiolytic drugs. In the plus maze test, the anxiolytic-like effect of diazepam (1.0 mg/kg) was blocked under both levels of nociception.


CONCLUSIONS
These data demonstrate that nociception modifies the response to anxiolytic drugs. The role of factors with anxiogenic properties produced during inflammation, which may modify diazepam and buspirone effects, is discussed.
Fernández-Guasti
A
A
Departamento de Farmacobiología, Centro de Investigación y Estudios Avanzados del IPN, Calz. de los Tenorios 235, Col. Granjas Coapa, Mexico, 14330, DF, Mexico. jfernand@mail.cinvestav.mx
Reyes
R
R
Martínez-Mota
L
L
López-Muñoz
F J
FJ
D000704:Analysis of Variance; D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001007:Anxiety / Q000188:drug therapy* / Q000503:physiopathology; D001241:Aspirin / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D002065:Buspirone / Q000008:administration & dosage / Q000627:therapeutic use*; D003975:Diazepam / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D007249:Inflammation / Q000139:chemically induced / Q000503:physiopathology; D007270:Injections, Intra-Articular; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D010146:Pain / Q000139:chemically induced / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D014527:Uric Acid
D014151:Anti-Anxiety Agents; D014527:Uric Acid; D003975:Diazepam; D001241:Aspirin; D002065:Buspirone
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