title: 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.
abstract: This experiment examined the effect of destroying central noradrenergic neurones using the selective neurotoxin N-(2-chloroethyl)-n-ethyl-2-bromobenzylamine (DSP4) on the acquisition of a temporal discrimination and on memory for duration, using a delayed conditional discrimination task. In phase I, rats that had received systemic treatment with DSP4 and vehicle-treated control rats were trained in a series of discrete trials to press lever A following a 2-s presentation of a light stimulus, and lever B following an 8-s presentation of the same stimulus. Following stimulus offset, a response on a panel placed midway between the two levers was required to initiate lever presentation; a single response on either lever resulted in withdrawal of both levers and, in the case of a "correct" response, reinforcer delivery. Both groups acquired accurate discrimination, achieving 90% correct choices within 50 sessions; the DSP4-treated group acquired accurate performance more slowly than the control group. In phase II, delays were interposed between stimulus offset and lever presentation in 50% of the trials. In the absence of a delay, discriminative accuracy was lower in the DSP4-treated group than in the control group. Accuracy declined as a function of post-stimulus delay in both groups; both groups showed a delay-dependent bias towards responding on lever A ("choose-short" bias). Neither of these effects differed significantly between the two groups. The concentrations of noradrenaline in the parietal cortex and hippocampus were reduced by 90% and 89% in the DSP4-treated group, compared to the levels in the control group, but the levels of dopamine, 5-hydroxytryptamine and 5-hydroxyindoleacetic acid did not differ significantly between the groups. The results confirm the deleterious effect of DSP4 on the acquisition of temporal discrimination, but do not provide evidence for a role of the noradrenergic innervation of the hippocampus and neocortex in temporal working memory.
authors.affiliation: Department of Psychiatry, University of Nottingham, Queen's Medical Centre, UK.
authors.forename: S S
authors.initials: SS
authors.lastname: al-Zahrani
authors.forename: A S
authors.initials: AS
authors.lastname: al-Ruwaitea
authors.forename: M Y
authors.initials: MY
authors.lastname: Ho
authors.forename: C M
authors.initials: CM
authors.lastname: Bradshaw
authors.forename: E
authors.initials: E
authors.lastname: Szabadi
mesh_terms: D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D000818:Animals; D001596:Benzylamines / Q000633:toxicity*; D001923:Brain Chemistry / Q000187:drug effects; D004193:Discrimination Learning / Q000187:drug effects*; D004192:Discrimination, Psychological / Q000187:drug effects*; D004298:Dopamine / Q000378:metabolism; D005260:Female; D008568:Memory / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects*; D009498:Neurotoxins / Q000633:toxicity*; D009638:Norepinephrine / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism / Q000502:physiology; D018490:Serotonin Agents / Q000494:pharmacology; D017603:Signal Detection, Psychological; D013998:Time Perception / Q000187:drug effects*
chemical_list: D001596:Benzylamines; D009498:Neurotoxins; D018490:Serotonin Agents; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; C012102:DSP 4; D004298:Dopamine; D009638:Norepinephrine