Different sensitivity to the motor incoordinating effects of gamma-hydroxybutyric acid (GHB) and baclofen in GHB-sensitive and GHB-resistant rats.
The present study investigated whether the differential sensitivity of selectively bred gamma-hydroxybutyric acid (GHB)-sensitive (GHB-S) and GHB-resistant (GHB-R) rats to GHB- and baclofen-induced sedation/hypnosis generalized to the motor incoordinating effect of the two drugs. To this aim, GHB-S and GHB-R rats were tested on a Rota-Rod after the acute administration of GHB (100-500 mg/kg, i.p.) and baclofen (1.25-5 mg/kg, i.p.). Significant line differences were observed in the dose-response curves for both GHB and baclofen, with GHB-S rats displaying a greater sensitivity to the motor incoordinating effects of both drugs than GHB-R rats. No line difference was observed in diazepam (1.25-5 mg/kg, i.p.), pentobarbital (5-15 mg/kg, i.p.), and ethanol (1-1.5 g/kg, i.p.) dose-response curves. These results suggest that the differential sensitivity of GHB-S and GHB-R rats to GHB and baclofen extends to the effects produced by doses of the two drugs which are 5-10 times lower than those for which rats have been selectively bred. These results are discussed in terms of the GABA(B) receptor being the likely neural substrate on which the differential sensitivity of GHB-S and GHB-R rats resides.
Lobina
Carla
C
Bernard B. Brodie Department of Neuroscience, University of Cagliari, Viale Diaz 182, I-09126 Cagliari, Italy.
Colombo
Giancarlo
G
Gessa
Gian Luigi
GL
Carai
Mauro A M
MA
D000704:Analysis of Variance; D000818:Animals; D001418:Baclofen / Q000494:pharmacology*; D001522:Behavior, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004351:Drug Resistance / Q000235:genetics*; D005260:Female; D018755:GABA Agonists / Q000494:pharmacology; D006885:Hydroxybutyrates / Q000494:pharmacology*; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D011597:Psychomotor Performance / Q000187:drug effects*; D051381:Rats; D045442:Rotarod Performance Test / Q000379:methods
D018755:GABA Agonists; D006885:Hydroxybutyrates; D006993:Hypnotics and Sedatives; C111420:4-hydroxybutyric acid; D001418:Baclofen