DSP4 and Herrnstein's equation: further evidence for a role of noradrenaline in the maintenance of operant behaviour by positive reinforcement

Abstract

The effect of the selective noradrenaline neurotoxin DSP4 on steady-state operant behaviour was examined using a quantitative behavioural paradigm based on Herrnstein's (1970) equation, which defines a hyperbolic relationship between steady-state response rate and reinforcement frequency in variable-interval schedules. Eleven rats received injections of DSP4 (two doses of 50 mg/kg, intraperitoneally), and 12 rats received injections of the vehicle alone. The rats were trained to steady state in a series of six variable-interval schedules of sucrose reinforcement, affording scheduled reinforcement frequencies of 4-360 reinforcers per hour. Herrnstein's equation was fitted to the data obtained from each rat and to the averaged data obtained from the two groups. The value of KH (the parameter expressing the reinforcement frequency needed to maintain the half-maximal response rate) was higher in the DSP4-treated rats than in the control rats; the value of Rmax (the parameter expressing the maximum response rate) did not differ significantly between the two groups. At the end of the behavioural experiment the rats were sacrificed for determination of the concentrations of catecholamines in the brain by high-performance liquid chromatography. The levels of noradrenaline in the parietal cortex, hippocampus and cerebellum of the DSP4-treated rats were less than 20% of those of the control rats. The results provide further evidence that central noradrenergic neurones are involved in the maintenance of operant behaviour by positive reinforcement.

Evidence for an involvement of 5-hydroxytryptaminergic neurones in the maintenance of operant behaviour by positive reinforcement

“…The proportion of the data variance accounted for by the equation (81-99 % of the data from individual subjects and more than 97 % of the group mean data) is comparable to that seen in previous experiments with rats using the present procedure (e.g. Bradshaw et al 1981 ;Morley et al 1987Morley et al , 1988. The fact that the values of p2 did not differ significantly between the two groups indicates that the 5,7-dihydroxytryptamineinduced lesion did not disrupt the hyperbolic relationship between response rate and reinforcement frequency specified by the equation.…”

“…It is therefore important to establish whether response rates maintained under the initial condition are recoverable upon re-exposure of the subjects to the same condition at the end of the experiment (see Catania and Reynolds 1968;Bradshaw et al 1981 ;Morley et al 1987Morley et al , 1988. In the present case a small but significant upward drift in response rates was observed (see Fig.…”

“…Finally, it is of interest to note that destruction of 5HTergic neurones had the opposite effect on the value of KH to that seen following destruction of noradrenergic neurones with 6-hydroxydopamine (Morley et al 1987) or N-(2-chlorethyl)-N-ethyt-2-bromobenzytamine (DSP4: Morley et al 1988). It has previously been proposed that the noradrenergic and 5HTergic pathways may play reciprocal roles in some behavioural functions (see Ogren 1985).…”

“…In order to encompass as wide a range of reinforcement frequencies as possible, we adopted the conventional procedure of terminating sessions either after a fixed time (30 rain) had elapsed or after a specified number of reinforcers had been delivered (e.g. Davison 1969;Bradshaw et al 1981;Alsop and Elliffe 1988;Morley et al 1988). (Restriction of the number of reinforcers that may be obtained in a session, which entails the use of short sessions in the case of high-density schedules, is necessary in order to prevent the confounding effect of satiation on response rate.)…”

Destruction of central noradrenergic neurones with DSP4 impairs the acquisition of temporal discrimination but does not affect memory for duration in a delayed conditional discrimination task

“…Although there was no effect of the lesion on the delay-dependent decline in overall accuracy of discrimination, the lesion resulted in the enhancement of a delay-dependent bias towards responding on the lever appropriate to the shorter duration ("chooseshort effect"), a characteristic feature of the performance of animals in delayed temporal discrimination tasks (Spetch and Wilkie 1983;Spetch and Rusak 1992). Several lines of evidence suggest that there is a functional interaction between noradrenergic and 5HTergic neurones in the brain (Brodie and Shore 1957;Leger and Descarries 1978;McRae-Degueurce et al 1985;Matsumoto et al 1995;Suzuki et al 1995), and manipulation of central noradrenergic and 5HTergic functions has been found to produce opposing effects on various behaviours, including unconditioned responses (Tanii et al 1993), locomotor behaviour (Kostrzewa et al 1994), electric-shock-induced burying behaviour (Lopez-Rubalcava and FernandezGuasti 1994), avoidance learning (Ogren 1985) and positively reinforced operant behaviour (Morley et al 1988;Wogar et al 1991). It was therefore of interest to see whether destruction of noradrenergic neurones with DSP4 would produce opposite effects on temporal discrimination learning and memory for duration to those produced by destruction of the 5HTergic pathways with 5,7-dihydroxytryptamine (cf.…”