Effect of destruction of the 5-hydroxytryptaminergic pathways on behavioural timing and "switching" in a free-operant psychophysical procedure

Abstract

This experiment examined the effect of destruction of the ascending 5-hydroxytryptaminergic (5HTergic) pathways on performance in a free-operant timing schedule. Rats received either injections of 5,7-dihydroxytryptamine into the dorsal and median raphe nuclei or sham lesions. 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 50 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. Response rate on lever B, expressed as a percentage of overall response rate, could be described by a two-parameter logistic function; neither the indifference point (i.e. the time corresponding to 50% responding on lever B) nor the slope of the function different between the two groups. However, the lesioned group showed a higher rate of switching between response alternatives than the sham-lesioned group. The levels of 5HT and 5-hydroxyindoleacetic acid were reduced in the brains of the lesioned rats, but the levels of noradrenaline and dopamine were not significantly altered. The results confirm previous findings that behaviour in timing schedules is sensitive to destruction of the central 5HTergic pathways, and suggest that these pathways may contribute to the inhibitory regulation of switching between behavioural states.

The effect of d -amphetamine on performance on two operant timing schedules

“…The pattern of responding seen in this experiment is consistent with numerous previous studies with this schedule (Stubbs 1976(Stubbs , 1979Bizo and White 1994a, 1994bAl-Zahrani et al 1996Chiang et al 1998Chiang et al , 1999. In both the "unconstrained-switching" and "con- Fig.…”

“…Significance of difference from vehicle treatment: *P<0.05 strained-switching" versions of the schedule, response rate on lever A declined and response rate on lever B increased during the course of the trial, this being reflected in an increasing percentage of total responding being devoted to lever B (%B) as the trial progressed. The relationship between %B and time within the trial was well described by a logistic function, the goodness of fit of the function seen in this experiment being similar to that seen in many previous studies (Bizo and White 1994a, 1994bAl-Zahrani et al 1996Chiang et al 1998Chiang et al , 1999. In this experiment, as in several previous studies (Fetterman and Killeen 1995;Al-Zahrani et al 1996Chiang et al 1998Chiang et al , 1999, there was a progressive decline in overall response rate during the course of the trial.…”

“…The relationship between %B and time within the trial was well described by a logistic function, the goodness of fit of the function seen in this experiment being similar to that seen in many previous studies (Bizo and White 1994a, 1994bAl-Zahrani et al 1996Chiang et al 1998Chiang et al , 1999. In this experiment, as in several previous studies (Fetterman and Killeen 1995;Al-Zahrani et al 1996Chiang et al 1998Chiang et al , 1999, there was a progressive decline in overall response rate during the course of the trial. The imposition of the constraint on switching resulted in a significant steepening of the slope of the psychophysical function and a reduction of the Weber fraction.…”

“…Although the constraint on switching had significant effects on the timing indices (most notably, reducing the Weber fraction: see above), damphetamine had similar effects on performance on both versions of the schedule. In this context, it may be noted that Al-Zahrani et al (1996) predicted that changes in the propensity to switch between operanda would be reflected in changes in T 50 under the "constrained switching" condition. However, Chiang et al (1999) recently found that central 5-HT depletion, which markedly increased switching rate under the "unconstrained switching" condition, failed to affect the value of T 50 under either the "constrained" or "unconstrained" versions of the task.…”

Evidence for the sensitivity of operant timing behaviour to stimulation of D1 dopamine receptors

“…This trend, which has been reported in several previous studies (e.g. Fetterman and Killeen 1995;Al-Zahrani et al 1996Chiang et al 1998), coincides with a gradual decline in overall response rate during the trial, a common finding in this schedule (Chiang et al 1998) and other related schedules (Fetterman and Killeen 1995;Stubbs 1976). It has been suggested that this may be due to a decay of arousal from a high level induced by the initial presentation of the operanda at the start of the trial (Killeen et al 1997; see also Killeen 1979).…”