EFFECT OF DESTRUCTION OF NORADRENERGIC NEURONS WITH DSP4 ON PERFORMANCE ON A FREE-OPERANT TIMING SCHEDULE

This experiment examined the effect of destroying central noradrenergi c neurones, using the selective neurotoxin DSP4 [N-(3-chloroethyl)-N-e thyl 2-bromobenzylamine], on performance in a free-operant timing sche dule. Rats received either systemic treatment with DSP4 or vehicle-alo ne injections. They were trained to press levers for a sucrose reinfor cer. Training sessions consisted of 40, 50-s trials in which reinforce rs were available on a variable-interval 25-s schedule; in the first 2 5 s of each trial, reinforcers were only available for responses on le ver A, whereas in the last 25 s reinforcers were available only for re sponses on lever B. Data were collected from probe trials (four per se ssion), in which no reinforcers were delivered, during the last ten of 60 training sessions. Both groups showed decreasing response rates on lever A, and increasing response rates on lever B, as a function of t ime from the onset of the trial. Quantitative indices of timing behavi our were derived from a two-parameter logistic function fitted to the relative response rates on lever B (response rate on lever B, expresse d as a percentage of overall response rate); this function accounted f or > 90% of the data variance in each group. The DSP4-treated group sh owed a significantly lower value of the indifference point (i.e. the t ime corresponding to 50% responding on lever B) than the control group . The slope of the function and the rate of switching between response alternatives did not differ significantly between the two groups. The concentrations of noradrenaline were markedly reduced in the neocorte x and hippocampus of the DSP4-treated group, but the concentrations of dopamine, 5-hydroxytryptamine and 5-hydroxyindoleacetic acid were not significantly altered. It is suggested that results may be consistent with a role of the dorsal ascending noradrenergic pathway in behaviou ral ''arousal''.