Abstract
The aim of the present study was to evaluate the effects of cholinergic receptor blockade in the rat prefrontal cortex on cognitive processes. The nicotinic antagonists neuronal bungarotoxin and dihydro-β-erythroidine and the muscarinic antagonist scopolamine were injected into the prelimbic area of the prefrontal cortex. Their behavioural effects were assessed in a T-maze to test reference memory (visual discrimination task) and working memory in delayed matching (MTS) and non-matching to sample (NMTS) tasks. Neuronal bungarotoxin produced a significant decrease in working memory performance in the MTS task but not in the NMTS task. In contrast, scopolamine impaired working memory in both MTS and NMTS tasks. Reference memory was not altered by any of the cholinergic antagonists. These results demonstrate a differential role of nicotinic and muscarinic receptors in the rat prefrontal cortex. Nicotinic transmission appears to be important in delayed response tasks requiring effortful processing for response selection, while the muscarinic system is involved in general working memory processes.
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Baddeley A (1992) Working memory. Science 255:556–559
Brito GNO, Brito LSO (1990) Septo-hippocampal system and the prelimbic sector of frontal cortex: a neuropsychological battery analysis in the rat. Behav Brain Res 36:127–146
Brito GNO, Thomas GJ, Davis BJ, Gingold SI (1982) Prelimbic cortex mediodorsal thalamus, septum and delayed alternation in rats. Exp Brain Res 46:52–58
Brito GNO, Silva SP, Brito LSO (1989) The cholinergic and dopaminergic systems of the prelimbic sector of frontal cortex and memory in the rat. Braz J Med Biol Res 22:1155–1158
Clarke PBS, Fibiger HC (1990) Reinforced alternation performance is impaired by muscarinic but not by nicotinic receptor blockade in rats. Behav Brain Res 36:203–207
Dehaene S, Changeux J-P (1989) Neuronal models of cognitive functions. Cognition 33:63–109
Decker MW, Majchrzak MJ (1992) Effects of systemic and intracerebroventricular administration of mecamylamine, a nicotinic cholinergic antagonist, on spatial memory in rats. Psychopharmacology 107:530–534
DiMattia BV, Kesner RP (1984) Serial position curves in rats: automatic versus effortful information processing. J Exp Psychol [Ann Behav Proc] 10:557–563
Dunnett SB, Roger DC, Jones GH (1989) Effects of nucleus basalis magnocellularis lesions in rats on delayed matching and non-matching to position tasks. Eur J Neurosci 1:395–406
Dunnett SB (1990) Role of the prefrontal cortex and striatal output systems in short-term memory deficits associated with ageing, basal forebrain lesions, and cholinergic-rich grafts. Can J Psychol 44:210–232
Dunnet SB, Wareham AT, Torres EM (1990) Cholinergic blockade in prefrontal cortex and hippocampus disrupts short-term memory in rats. Neuroreport 1:61–64
Fuster JM (1989) The prefrontal cortex. Anatomy, physiology and neuropsychology of the frontal lobe. Raven Press, New York
Goldman-Rakic PS (1990) Cortical localization of working memory. In: Gaugh JL, Weingerger NM, Lynch G (eds) Brain organization and memory: cells, systems and circuits. Oxford University Press, New York
Granon S, Vidal C, Thinus-Blanc C, Changeux J-P, Poucet B (1994) Working memory, response selection, and effortful processing in rats with medial prefrontal lesions. Behav Neurosci 108:883–891
Gray JA, Mitchell SN, Joseph MH, Grigoryan GA, Dawe S, Hodges H (1994) Neurochemical mechanisms mediating the behavioral and cognitive effects of nicotine. Drug Dev Res 31:3–17
Groenewegen HJ (1988) Organization of the efferent connections of the mediodorsal thalamic nucleus in the rat, related to the mediodorsal-prefrontal topography. Neuroscience 24:379–431
Hasher L, Zacks RT (1979) Automatic and effortful processes in memory. J Exp Psychol [Gen] 108:356–388
Hodges H, Allen Y, Sinden J, Lantos P L, Gray J A (1991) Effects of cholinergic-rich neural grafts on radial maze performance of rats after excitotoxic lesions of the forebrain cholinergic projection system. II. Cholinergic drugs as probes to investigate lesion-induced deficits and transplant-induced functional recovery. Neuroscience 45:609–623
Isseroff A, Rosvold HE, Galkin TW, Goldman-Rakic PS (1982) Spatial memory impairments following damage to the mediodorsal nucleus of the thalamus. Brain Res 232:97–113
Knight RT (1994) Attention regulation and human prefrontal cortex. In: Thierry A-M, Glowinski J, Goldman-Rakic PS, Christen Y (eds) Motor and cognitive functions of the prefrontal cortex. Springer-, Berlin Heidelberg, pp 160–173
Kolb B (1990) Prefrontal cortex. In: Kolb B, Tees RC (eds) The cerebral cortex of the rat MIT Press, Cambridge MA, pp 437–471
Krettek JE, Price JL (1977) The cortical projections of the mediodorsal nucleus and adjacent thalamic nuclei in the rat. J Comp Neurol 171:157–192
Levin ED (1992) Nicotinic systems and cognitive function. Psychopharmacology 108:417–431
Levin ED, Castonguay M, Ellison G (1987) Effects of the nicotinic receptor blocker, mecamylamine, on radial-arm maze performance in rats. Behav Neural Biol 48:206–212
Loring RH, Zigmond RE (1988) Characterization of neuronal nicotinic receptors by snake venom neurotoxins. Trends Neurosci 11:73–78
Markowitsch HJ (1982) Thalamic mediodorsal nucleus and memory: a critical evaluation of studies in animals and man. Neurosci Biobehav Rev 6:351–380
Mc Gurck SR, Levin ED, Butcher LL (1991) Impairment of radialarm maze performance in rats following lesions involving the cholinergic medial pathway: reversal by arecoline and differential effects of muscarinic and nicotinic antagonists. Neuroscience 44:137–147
Milner B, Petrides M (1984) Behavioural effects of frontal lobe lesions in man. Trends Neurosci 7:403–407
Moran PM (1993) Differential effects of scopolamine and mecamylamine on working and reference memory in the rat. Pharmacol Biochem Behav 45:533–538
Muir JL, Dunnett SB, Robbins TW, Everitt BJ (1992) Attentional functions of the forebrain cholinergic systems: effects of intraventricular hemicholinium, physostigmine, basal forebrain lesions and intracortical grafts on a multiple-choice serial reaction time task. Exp Brain Res 89:611–622
Muir JL, Everitt BJ, Robbins TW (1994) AMPA-induced excitotoxic lesions of the basal forebrain: a significant role for the cortical cholinergic system in attentional function. J Neurosci. 14:2313–2326
Mulle C, Vidal C, Benoit P, Changeux JP (1991) Existence of different subtypes of nicotinic AchRs in the rat habenulo-interperdoncular system. J Neurosci 11:2588–2597
Newhouse P, Sunderland T, Tariot P, Blumhardt C, Weingartner H, Mellow W (1988) Intravenous nicotine in Alzheimer's disease: a pilot study. Psychopharmacology 95:171–175
Olton DS, Wenk G, Church RM, Meck WH (1988) Attention and the frontal cortex as examined by simultaneous temporal processing. Neuropsychologia 26:307–318
Pardo JV, Fox PT, Raichle ME (1991) Localization of a human system for sustained attention by positron emission tomography. Nature 349:61–64
Poucet B (1990) A further characterization of the spatial problem-solving deficit induced by lesions of the medial frontal cortex in the rat. Behav Brain Res 41:229–237
Robbins TW, Everitt BJ, Marston HM, Wilkinson J, Jones GH, Page KJ (1989) Comparative effects of ibotenic acid-and quisqualic acid-induced lesions of the substantia innominata on attentional function in the rat: further implications for the role of the cholinergic neurons of the nucleus basalis in cognitive processes. Behav Brain Res 35:221–240
Roberts AC, Robbins TW, Everitt BJ, Muir JL (1992) A specific form of cognitive rigidity following excitotoxic lesions in the basal forebrain in marmosets. Neuroscience 47:251–264
Rouanet H, Lépine D (1970) Comparison between treatments in a repeated measurement design; ANOVA and multivariate methods. Brain J Math Stat Psychol 23:146–163
Sahakian B, Jonnes G, Levy R, Gray J, Warburton D (1989) The effects of nicotine on attention, information processing, and short-term memory in patients with dementia of the Alzheimer type. Br J Psychiatry 154:797–800
Sahakian BJ, Owen AM, Morant NJ, Eagger SA, Boddington S, Crayton L, Crockford H A, Crooks M, Hill K, Levy R (1993) Further analysis of the cognitive effects of tetrahydroaminoacridine (THA) in Alzheimer's disease: assessment of attentionnal and mnemonic function using CANTAB. Psychopharmacology 110:395–401
Schneider W, Shiffrin RM (1977) Controlled and automatic information processing: I detection, search and attention. Psychol Rev 84:1–66
Squire LR (1987) Memory and brain. Oxford University Press, New York
Stokes KA, Best PJ (1990) Response biases do not underlie the radial maze deficit in rats with mediodorsal thalamus lesions. Behav Neurol Biol 53:334–345
Uylings HBM, Van Eden CG (1990) Qualitative and quantitative comparison of the prefrontal cortex in rat and in primates, including humans. Prog Brain Res 85:31–62
Vidal C (1994) Nicotinic potentiation of glutamatergic synapses in the prefrontal cortex: new insight into analysis of the role of nicotinic receptors in cognitive functions. Drug Dev Res 31:120–126
Vidal C, Changeux J-P (1989) Pharmacological profile of nicotinic acetylcholine receptors in the rat prefrontal cortex: an electrophysiological study in a slice preparation. Neuroscience 29:261–270
Vidal C, Changeux JP (1993) Nicotinic and muscarinic modulations of excitatory transmission in the rat prefrontal cortex in vitro. Neuroscience 56:23–32
Voytko ML, Olton DS, Richardson RT, Gorman LK, Tobin JR, Price DL (1994) Basal forebrain lesions in monkeys disrupt attention but not learning and memory. J Neurosci 14:157–186
Wesnes K, Warburton DM (1984) Effects of scopolamine and nicotine on human rapid information processing performance. Psychopharmacology 82:147–150
Zilles K (1985) The cortex of the rat. A stereotaxic atlas. Springer, Berlin
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Granon, S., Poucet, B., Thinus-Blanc, C. et al. Nicotinic and muscarinic receptors in the rat prefrontal cortex: Differential roles in working memory, response selection and effortful processing. Psychopharmacology 119, 139–144 (1995). https://doi.org/10.1007/BF02246154
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DOI: https://doi.org/10.1007/BF02246154