Impaired acquisition of temporal differentiation performance following lesions of the ascending 5-hydroxytryptaminergic pathways

Abstract

Nineteen rats received injections of 5,7-dihydroxytryptamine into the dorsal and median raphe nuclei; 16 rats received sham injections. The rats underwent 50 daily training sessions under an interresponse-time-greater-than-15-seconds (IRT greater than 15 s) schedule of sucrose reinforcement. The lesioned group showed impaired acquisition of temporal differentiation, in that their response rates remained significantly higher and their obtained reinforcement frequencies significantly lower than those of the control (sham-lesioned) group. Comparison of the IRT frequency distributions obtained from the two groups during the last 5 days of training showed that the lesioned group produced a significantly higher proportion of very short IRTs (less than 3 s) than the control group; when these short IRTs were disregarded, the lesioned group displayed a significantly lower mean IRT and a significantly higher coefficient of variation than the control group. The levels of 5-hydroxytryptamine (5HT) and 5-hydroxyindoleacetic acid in the parietal cortex, hippocampus, amygdala, nucleus accumbens and hypothalamus were markedly reduced in the lesioned group, but the levels of noradrenaline and dopamine were not significantly affected by the lesion. The results suggest that destruction of the ascending 5HTergic pathways may reduce animals' capacity to inhibit positively reinforced operant behaviour, and may impair temporal discrimination.

Behavioural and physiological correlates of impulsivity in the domestic dog (Canis familiaris)

“…Laboratory models of impulsivity in non human animals also tend to focus on response inhibition and delayed reward paradigms [19]. Response inhibition models assess the subject"s ability to inhibit responding [20], [21], [22], and delayed reward models measure an animal"s choice between a small, immediate reinforcer, and a large, delayed reinforcer, assessing "impulsive choice", an index of impulsivity [23], [24]. Van den Bergh et al [25] investigated the relationship between response inhibition and delay aversion in rats, suggesting that response inhibition and delay aversion are independent measures of impulsivity, consistent with previous findings in humans [18].…”

Effect of lesions of the ascending 5-hydroxytryptaminergic pathways on timing behaviour investigated with the fixed-interval peak procedure

“…The levels of 5-hydroxytryptamine (5HT) and 5-hydroxyindoleacetic acid in the parietal cortex, hippocampus, amygdala, nucleus accumbens and hypothalamus were markedly reduced in the lesioned group, but the levels of noradrenaline and dopamine were not significantly affected by the lesion. The results confirm the involvement of 5HTergic function in timing behaviour.Key words: 5-Hydroxytryptamine -5,7-Dihydroxytryptamine -Operant behaviour -Timing -Fixed-interval peak procedure -Rat There is increasing evidence for an involvement of the ascending 5-hydroxytryptaminergic (5HTergic) pathways in the regulation of positively reinforced operant Altman et al 1990;Wogar et al 1991Wogar et al , 1992Wogar et al , 1993aMorrissey et al 1993). Schedules in which the passage of time serves as a controlling variable may be especially sensitive to the effects of such lesions.…”

“…Performance maintained under these schedules is characterized by low response rates and an IRT frequency distribution having a mode approximating the criterion IRT (t). We found that destruction of the 5HT pathways was associated with a shift of the IRT distribution in favour of shorter IRTs, and an increase in the coefficient of variation (SD/mean IRT) of the distribution (Wogar et al 1992(Wogar et al , 1993b. As the coefficient of variation has been regarded as an expression of the Weber fraction for time intervals (see Catania 1970), this result raised the possibility that the lesion impaired the rat's ability to discriminate the passage of time.…”

“…Schedules in which the passage of time serves as a controlling variable may be especially sensitive to the effects of such lesions. For example, in a recent series of experiments (Wogar et al 1992(Wogar et al , 1993bMorrissey et al 1993) we examined the effect of destruction of the 5HTergic pathways on performance in two different timing paradigms, an interresponse-timegreater-than-t (IRT > t) schedule and an interval bisection procedure. In both cases the lesion significantly altered performance; however, the pattern of disruption differed between the two procedures (see below).…”

Serotonin Depletion Impairs Waiting but not Stop-Signal Reaction Time in Rats: Implications for Theories of the Role of 5-HT in Behavioral Inhibition

“…For example, 5-HT depletion (produced by either i.c.v. or intra-raphé 5,7-DHT infusion) profoundly and permanently increased premature responses in the 5-CSRT task (Carli and Samanin, 2000;Harrison et al, 1997;Winstanley et al, 2004a, b), and increased responding (decreased correctly completed trials) (Fletcher, 1995) and decreased inter-response times (Wogar et al, 1992) during DRL schedules. Recent studies have shown that although 5-HT receptors are very strongly implicated in premature response control on the 5-CSRT task, the nature of this control over the ability to wait is complex, being both receptor-subtype-and site-dependent (Carli et al, 2006; Robinson et al, 2007;Winstanley et al, 2004bWinstanley et al, , 2006.…”