Long-term daily use of @entity15221 ( @entity2933 ) and related compounds has recently been associated with a @entity3347 . To the best of the authors' knowledge, there are currently no animal models of @entity2933 withdrawal. OBJECTIVES: The authors studied and described the effect of chronic dosing of @entity2933 (3-6 days) on tolerance and withdrawal in a @entity35 model. METHODS: @entity35 were administered @entity2933 every three hours via intraperitoneal catheter. Groups of @entity35 (2 per group) were dosed with @entity2933 for either 3 (24 doses), 4 (32 doses), 5 (40 doses), or 6 (48 doses) days. The @entity2933 dose was 0.25 g/kg for doses 1-8, 0.75 g/kg for doses 9-12, 1 g/kg for doses 13-16, 1.25 g/kg for doses 17-24, 1.5 g/kg for doses 25-32, 1.75 g/kg for doses 33-40, and 2 g/kg for doses 41-48. Following the last dose of @entity2933 , the @entity35 were scored using a 16-point @entity1068 intoxication-withdrawal scale rating spontaneous behaviors, response to handling, grooming, and neurological signs. Lower scores indicate intoxication, while higher scores indicate withdrawal. Scores were recorded at hours 0, 1, 2, 3, 4, 5, 6, 9, 12, and 24. RESULTS: Tolerance: @entity35 dosed with @entity2933 for more days were less intoxicated one hour after their last @entity2933 dose despite receiving higher doses. WITHDRAWAL: The scores for all @entity35 dosed with @entity2933 increased at hours 4 (p = 0.028), 5 (p = 0.037), 6 (p = 0.007), and 9 (p = 0.024) after the last dose, indicating withdrawal. The scores demonstrated a linear increase dependent upon the number of days of @entity2933 dosing at hours 3 (p < 0.000), 4 (p = 0.004), 5 (p = 0.002), and 12 (p = 0.039) as well as prior to the last dose at hour 0 (p = 0.000). No @entity35 developed @entity410 . CONCLUSIONS: Tolerance and mild withdrawal in @entity35 can be induced by administering intraperitoneal @entity2933 every three hours for 3-6 days. More prolonged dosing and higher doses of @entity2933 may be necessary to induce severe withdrawal.

Gamma-hydroxybutyric acid tolerance and withdrawal in a XXXX model.

@entity3347 :: ('MESH:D013375', 'Disease') :: ['withdrawal syndrome'] @entity410 :: ('MESH:D012640', 'Disease') :: ['seizures'] @entity15221 :: ('MESH:D012978', 'Chemical') :: ['gamma-hydroxybutyrate'] @entity2933 :: ('CHEBI:30830', 'Chemical') :: ['GHB'] @entity35 :: ('10116', 'Species') :: ['rat', 'Rats', 'rats'] @entity1068 :: ('MESH:D000431', 'Chemical') :: ['ethanol']
@entity35 :: (10116,Species) :: ['rat']
