Peter Prior

Date of Award


Degree Type


Degree Name

Doctor of Philosophy


These experiments concerned potential interactions of the cholinergic with the noradrenergic or serotonergic systems, in rat working and reference memory (WM & RM). In experiment 1a, 63 rats were trained to collect reinforcement from a radial maze, with eight of 16 arms consistently reinforced. Working errors (WEs) were re-entries into baited arms visited within a session; reference errors (REs) were visits to never-baited arms. The rats then participated in a dose-response study of scopolamine (scop). Correct entries decreased; WEs and REs increased concomitantly with dose. Cholinergic systems may not subserve WM specifically. Forty-one of these rats participated a year later in experiment 1b, after reacquisition of the same task. Rats were pretreated with one of vehicle, DSP4, or PCPA. Thirty min before final testing, they received, i.p., one of saline (SAL), 1.0 mg/kg scop, or 1.0 mg/kg methylscopolamine (mscop). DSP4 reduced forebrain noradrenaline (NA) level. PCPA depleted 5HT and moderately reduced NA level. DSP4+mscop and PCPA+mscop did not affect performance. Scop, DSP4+scop, and PCPA+scop decreased correct responses. PCPA+scop also reduced WEs, apparently ameliorating WM, but probably due to a confound. Correct responses correlated with serotonin, and errors, with noradrenaline. In experiment 2a, 2b, and 3, rats were trained to collect reinforcement from cups in an open field surface, of which five out of 10 were reinforced. WEs were within-session revisits to a reinforced cup. REs were visits to never-reinforced cups. In experiment 2a, 69 rats trained in this participated in a scop dose-response study. Correct choices decreased with dose, and correlated with locomotor variables measured in an automated monitor. Errors did not increase. Accuracy was probably impaired by CNS cholinergic blockade, and may have been influenced by locomotor factors. In experiment 2b, the same sample was pretreated with PCPA or vehicle. Before testing, they received SAL, scop or mscop. PCPA depleted 5HT, and moderately reduced NA levels. PCPA+1.0 mg/kg scop reduced correct responses. Effects of scop and PCPA may have interacted to impair open field performance, with no amelioration of WM. Correlations distinguished locomotion, related to serotonin, from errors, related to catecholamines. Experiment 3 tested the results of experiment 2b, which showed no effect of scop alone. After acquisition, 87 rats were pretreated with PCPA or vehicle. Prior to a final test, they received SAL, mscop, or scop. Scop and PCPA+scop decreased the number correct; PCPA+scop increased both WEs and REs. Cholinergic and one or more neurochemical effects of PCPA may have interacted to increase errors, without respect to memory type. In summary, WEs and REs could be increased concomitantly with cholinergic blockade alone or combined with PCPA. These data are contrary to hypotheses that WM and RM are subserved by different neurochemical systems.



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