Effect of destruction of noradrenergic neurones with DSP4 on performance on a free-operant timing schedule

Abstract

This experiment examined the effect of destroying central noradrenergic neurones, using the selective neurotoxin DSP4 [N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine], on performance in a free-operant timing schedule. Rats received either systemic treatment with DSP4 or vehicle-alone injections. They were trained to press levers for a sucrose reinforcer. Training sessions consisted of 40, 50-s trials in which reinforcers were available on a variable-interval 25-s schedule; in the first 25 s of each trial, reinforcers were only available for responses on lever A, whereas in the last 25 s reinforcers were available only for responses on lever B. Data were collected from probe trials (four per session), 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 time from the onset of the trial. Quantitative indices of timing behaviour were derived from a two-parameter logistic function fitted to the relative response rates on lever B (response rate on lever B, expressed as a percentage of overall response rate); this function accounted for > 90% of the data variance in each group. The DSP4-treated group showed a significantly lower value of the indifference point (i.e. the time 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 neocortex 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 behavioural "arousal".

Fos expression in the orbital prefrontal cortex after exposure to the fixed-interval peak procedure

“…Response rate declined rapidly from an initially high level at the start of the trial, and a relatively constant rate of responding was maintained throughout the remainder of the trial. The initial decline of response rate has been observed previously in experiments in which VI schedules have been presented in discrete trials [28–31], and has been attributed to a reduction of arousal from a high level occasioned by the initial presentation of the operandum at the start of the trial [32].…”

Effect of central 5-hydroxytryptamine depletion on performance in the free-operant psychophysical procedure: facilitation of switching, but no effect on temporal differentiation of responding

“…In this experiment, as in some previous experiments (Fetterman and Killeen 1995;Al-Zahrani et al 1996, there was a progressive decline in overall response rate during the course of the trial. Killeen et al (1997) have suggested that this intra-trial decline in response rate may reflect a progressive reduction of arousal from a high level occasioned by the initial presentation of the operanda at the start of the trial (see also Al-Zahrani et al 1998).…”

Differential effects of methamphetamine and haloperidol on the control of an internal clock.

“…Indeed, in our experiments, MAP shifted the peak time in opposite directions in probe trials with or without gaps—indicative of both clock and attentional effects—whereas HAL shifted the peak time significantly in trials with gaps, but only marginally in trials without gaps—indicative of predominantly an attentional effect rather than a clock-speed effect. On the other hand, results might have been due to the activation of the noradrenergic (Al-Zahrani, Al-Ruwaitea, Ho, Bradshaw, & Szabadi, 1998) or serotonergic systems (Chiang, Al-Ruwaitea, Ho, Bradshaw, & Szabadi, 1999). Additional pharmacological, neurophysiological and genetic manipulations using the behavioral paradigms described here will help elucidate the biological substrates of the attentional mechanisms of interval timing.…”