RATIONALE: REM sleep deprivation (REMSD) has been shown to increase rates of free-operant avoidance responding. Depletion of 5-hydroxytryptamine (5-HT, serotonin) levels produces similar effects on responding. OBJECTIVE: We studied whether the pharmacological activation of the 5-HT1A receptor would produce effects on avoidance responding similar to REMSD and depleted 5-HT levels. METHODS: Rats were trained to lever press on a free-operant avoidance task. Dose-effect functions were established for 8-OH-DPAT (a 5-HT1A receptor agonist) (0.1-1.0 mg/kg) and WAY 100635 (a 5-HT1A receptor antagonist) (0.1-1.0 mg/kg). Rats were then exposed to REMSD (48 h) or equivalent control conditions, and then administered 8-OH-DPAT (0.6 mg/kg) and/or WAY 100635 (0.025-0.1 mg/kg). RESULTS: Injections of 8-OH-DPAT increased rates of avoidance responding in a dose-dependent manner, while WAY 100635 did not alter responding. The effect of 8-OH-DPAT was antagonized by pre-injection of WAY 100635. REMSD and injections of 8-OH-DPAT increased rates of avoidance responding and the effects of both manipulations were reversed by pre-injection of WAY 100635. CONCLUSIONS: Activation of the 5-HT1A receptor may be a mechanism by which REMSD increases rates of free-operant avoidance responding.
RATIONALE: REM sleep deprivation (REMSD) has been shown to increase rates of free-operant avoidance responding. Depletion of 5-hydroxytryptamine (5-HT, serotonin) levels produces similar effects on responding. OBJECTIVE: We studied whether the pharmacological activation of the 5-HT1A receptor would produce effects on avoidance responding similar to REMSD and depleted 5-HT levels. METHODS:Rats were trained to lever press on a free-operant avoidance task. Dose-effect functions were established for 8-OH-DPAT (a 5-HT1A receptor agonist) (0.1-1.0 mg/kg) and WAY 100635 (a 5-HT1A receptor antagonist) (0.1-1.0 mg/kg). Rats were then exposed to REMSD (48 h) or equivalent control conditions, and then administered 8-OH-DPAT (0.6 mg/kg) and/or WAY 100635 (0.025-0.1 mg/kg). RESULTS: Injections of 8-OH-DPAT increased rates of avoidance responding in a dose-dependent manner, while WAY 100635 did not alter responding. The effect of 8-OH-DPAT was antagonized by pre-injection of WAY 100635. REMSD and injections of 8-OH-DPAT increased rates of avoidance responding and the effects of both manipulations were reversed by pre-injection of WAY 100635. CONCLUSIONS: Activation of the 5-HT1A receptor may be a mechanism by which REMSD increases rates of free-operant avoidance responding.
Authors: David R Thomas; Sergio Melotto; Mario Massagrande; Andrew D Gribble; Phillip Jeffrey; Alexander J Stevens; Nigel J Deeks; Peter J Eddershaw; Susan H Fenwick; Graham Riley; Tania Stean; Claire M Scott; Matthew J Hill; Derek N Middlemiss; Jim J Hagan; Gary W Price; Ian T Forbes Journal: Br J Pharmacol Date: 2003-06 Impact factor: 8.739