Abstract
An operant task for the measurement of sustained attention or vigilance in rats was characterized. The task requires the animals to respond to the presentation of visual signals (presented for 25, 50, or 500 ms) by operating one lever (“hits”) and to the absence of a signal by operating the opposite lever (“correct rejection”). Incorrect responses (“misses” and “false alarms”, respectively) were not rewarded. Performance in this task is a function of signal length, i.e., the shorter the signals the higher the number of misses. An increase in “background noise” by flashing the chamber houselight (at 0.5 Hz) impaired the animals' ability to discriminate between signal and nonsignal events. Also, flashing the houselight augmented the vigilance decrement observed for shortest signals. An increase in the event-rate also resulted in a vigilance decrement. Finally, the inability of the animals to time signals was examined by testing the effects of an increase in event asynchrony. In a second experiment, the performance of differently aged rats (6- and 20 month-old male BNNia/F344 rats) was studied. Compared to young animals, 20-month-old rats showed a decrease in their ability to discriminate between shortest signals (25 ms) and non-signal events but did not differ in their ability to correctly reject nonsignal trials. Administration of the benzodiazepine receptor (BZR) agonist chlordiazepoxide (CDP; 3, 5, 8 mg/kg) resulted in an impairment of the animals' ability to discriminate between signal and non-signal events and, similar to the effects of age, this effect was exclusively due to an increase in the number of misses. CDP generally produced potent effects while affecting the aged animals to a greater degree. BZR-ligands with weak or “selective” inverse agonist properties (ZK 93426;β-CCtB) did not affect vigilance performance. The BZR partial inverse agonist RU 33965 (0.1, 0.5 mg/kg) dose-dependently impaired vigilance performance. The administration of amphetamine (0.4, 0.8 mg/kg) also impaired performance, but these impairments were possibly based on effects unrelated to attentional mechanisms. The finding that performance in this task revealed the interactions between the effects of age and BZR agonists on attentional abilities further supports the validity of measures of performance generated by this task.
Similar content being viewed by others
References
Altavista MC, Rossi P, Bentivoglio AR, Crociani P, Albanese A (1990) Aging is associated with a diffuse impairment of forebrain cholinergic neurons. Brain Res 508:51–59
Andrews JS, Grützner M, Stephens DN (1992) Effects of cholinergic and non-cholinergic drugs on visual discrimination and delayed visual discrimination performance in rats. Psychopharmacology 106:523–530
Armstrong DM, Sheffield R, Buzsaki G, Chen K, Hersh LB, Nearing B, Gage FH (1993) Morphological alterations of choline acetyltransferase-positive neurons in the basal forebrain of aged behaviorally characterized Fisher 344 rats. Neurobiol Aging 14:457–470
Aston-Jones G, Rogers J, Shaver RD, Dinan TG, Moss DE (1985) Age-impaired impulse flow from nucleus basalis to cortex. Nature 318:462–464
Baddeley AD, Colquhoun WP (1969) Signal probability and vigilance: a reappraisal of the “signal rate” effect. Br J Psychol 60:169–178
Bruno JP, Moore H, Dudchenko P, Sarter M (1992) Modulation of frontal cortical acetylcholine release by benzodiazepine receptor ligands: age-dependent effects and behavioral correlates. In: Meyer EM, Simpkins JW, Yamamoto J, Crews FT (eds) Treatment of the dementias: a new generation of progress. Plenum Press, New York, pp 277–298
Bruno JP, Moore H, Stuckman S, Johnson B, Sarter M (1994) Repeated microdialysis sampling as a valid technique to study cortical and striatal acetylcholine efflux. Curr Sep 13:25–29
Bushnell PJ, Kelly KL, Crofton KM (1994) Effects of toluene inhalation on detection of auditory signals in rats. Neurotoxicol Teratol 16:149–160
Callahan MJ, Kinsora JJ, Harbaugh RE, Reeder TM, Davis RE (1993) continuous ICV infusion of scopolamine impairs sustained attention of rhesus monkeys. Neurobiol Aging 14:147–151
Castleden CM, George CF, Marcher D, Hallett C (1977) Increased sensitivity to nitrazepam in old age. BMJ 1:10–12
Clark CR, Geffen GM, Geffen LB (1987) Catecholamines and attention II: pharmacological studies in normal humans. Neurosci Biobehav Rev 11:353–364
Cole BJ, Robbins TW (1987) Amphetamine impairs the discriminative performance of rats with dorsal noradrenergic bundle lesions on a 5-choice serial reaction time task: New evidence for central dopaminergic-noradrenergic interactions. Psychopharmacology 91:458–466
Cole SE (1986) Dose-dependent impairment in the performance of a go-no go successive discrimination by chloridazepoxide. Psychopharmacology 88:184–186
Colquhoun WP, Baddeley AD (1967) Influence of signal probability during pretraining on vigilance decrement. J Exp Psychol 73:153–155
Craig A (1987) Signal detection theory and probability matching apply to vigilance. Hum Fact 29:645–652
Craik FIM, Byrd M (1982) Aging and cognitive deficits. The role of attentional resources. In: Craik FIM, Trehub S (eds) Aging and cognitive processes. Plenum Press, New York, pp 191–211
Craik FIM, Simon E (1980) Age differences in memory: the roles of attention and depth processing. In: Poon LW, Fozard JL, Cermak LS, Arenberg D, Thompson LW (eds) New directions in memory and aging. Hillsdale, Erlbaum, pp 95–111
Curran HV (1991) Antianxiety treatments and human memory. In: Briley M, File SE (eds) New concepts in anxiety. CRC Press, Boca Raton, pp 395–405
Curran HV, Birch B (1991) Differentiating the sedative, psychomotor and amnesic effects of benzodiazepines: a study with midazolam and the benzodiazepine antagonist, flumazenil. Psychopharmacology 103:519–523
Deacon RMJ, Budhram P, Dawson D, Galliani G, Guy AP, Gardner CR (1990) Investigation of potential cognition enhancing properties of RU 33965, a benzodiazepine receptor partial inverse agonist. Psychopharmacology 101:S14
Dudchenko P, Paul B, Sarter M (1992) Dissociation between the effects of benzodiazepine receptor agonists on behavioral vigilance and responsivity. Psychopharmacology 109:203–211
Dudchenko P, Gordon B, Sarter M (1994) Effects of benzodiazepine receptor ligands on simultaneous visual discriminations of variable difficulty. J Psychopharmacology 8:141–147
Duka T, Redemann B, Mager T, Voet B (1993) Scopolamine as a pharmacological tool to study memory processes: application of a cognition enhancer. Soc Neurosci Abstr 19:507.5
Evenden JL, Robbins TW (1983) Increased response switching, perseveration and perseverative switching following d-amphetamine in the rat. Psychopharmacology 80:67–73
Evenden JL, Robbins TW (1985) The effects ofd-amphetamine, chlordiazepoxide and alpha-flupenthixol on food-reinforced tracking of a visual stimulus by rats. Psychopharmacology 85:361–366
Evenden JL, Turpin M, Oliver L, Jennings C (1993) Caffeine and nicotine improve visual tracking by rats: a comparison with amphetamine, cocaine and apomorphine. Psychopharmacology 110:169–176
Fisch HU, Baktir G, Karlaganis G, Minder C, Bircher J (1990) Excessive motor impairment two hours after Triazolam in the elderly. Eur J Clin Pharmacol 38:229–232
Fischer W, Chen K, Gage FH, Björklund A (1991a) Progressive decline in spatial learning and integrity of forebrain cholinergic neurons in rats during aging. Neurobiol Aging 13:9–23
Fischer W, Nilsson OG, Björklund A (1991b) In vivo acetylcholine release as measured by microdialysis is unaltered in the hippocampus of cognitively impaired aged rats with degenerative changes in the basal forebrain. Brain Res 556:44–52
Francis RL, Cooper SJ (1979) Chlordiazepoxide-induced disruption of discrimination behaviour: a signal detection analysis. Psychopharmacology 63:307–310
Frey PW, Colliver JA (1973) Sensitivity and responsivity measures for discrimination learning. Learn Motiv 4:327–342
Gardner CR, Tully RG, Hedgecock JR (1993) The rapidly expanding range of neuronal benzodiazepine receptor ligands. Progr Neurobiol 40:1–61
Gentil V, Gorenstein C, Camargo CHP, Singer JM (1989) Effects of flunitrazepam on memory and their reversals by two antagonists. J Clin Psychopharmacol 9:191–197
Gordon B, Carson K (1990) The basis for choice reaction time slowing in Alzheimer's disease. Brain Cogn 13:148–166
Greenblatt DJ, Harmatz JS, Shapiro L, Englehardt N, Gouthro TA, Shader RI (1991) Sensitivity to triazolam in the elderly. N Engl J Med 324:1691–1698
Grilly DM, Nocjar C (1990) Cocaine and vigilance task performance of rats: effects of delay of reinforcement. Pharmacol Biochem Behav 37:643–648
Grilly DM, Gowans GC, McCann DS, Grogan TW (1989) Effects of cocaine andd-amphetamine on sustained and selective attention in rats. Pharmacol Biochem Behav 33:733–739
Hodges H, Thrasher S, Gray JA (1989) Improved radial maze performance induced by the benzodiazepine receptor antagonist ZK 93426 in lesioned and alcohol-treated rats. Behav Pharmacol 1:45–55
Hoffman WE, Albrecht RF, Miletich DJ, Hagen TJ, Cook JM (1986) Cerebrovascular and cerebral metabolic effects of physostigmine, midazolam, and a benzodiazepine antagonist. Anesth Analg 65:639–644
Holley LA, Dudchenko P, Sarter M (1992) Attenuation of muscarinic receptor blockade-induced impairment of spatial delayed alternation performance by the triazole MDL 26,479. Psychopharmacology 109:223–230
Holley LA, Miller JA, Chmielewski P, Dudchenko P, Sarter M (1993) Interactions between the effects of basal forebrain lesions and chronic treatment with MDL 26,479 on learning and markers of cholinergic transmission. Brain Res 610:181–193
Holley LA, Wiley RG, Lappi DA, Sarter M (1994) Cortical cholinergic deafferentation following the intracortical infusion of 192 IgG-saporin: a quantitative histochemical study. Brain Res, in press
Jensen LH, Petersen EN, Braestrup C, Honoré T, Kehr W, Stephens DN, Schneider H, Seidelmann D, Schmiechen R (1984) Evaluation of theβ-carboline ZK 93426 as a benzodiazepine receptor antagonist. Psychopharmacology 83:249–256
Koelega HS (1989) Benzodiazepines and vigilance performance: a review. Psychopharmacology 98:145–165
Koelega HS (1993) Stimulant drugs and vigilance performance: a review. Psychopharmacology 111:1–16
Komiskey HI, Buck MA, Mundinger KL, McSweeney FK, Farmer-Dougan VA, Dougan JD (1987) Effect of aging on anticonflict and CNS depressant activity of diazepam in rats. Psychopharmacology 93:443–448
Kroboth PD, McAuley JW, Smith RB (1990) Alprazolam in the elderly: pharmacokinetics and pharmacodynamics during multiple dosing. Psychopharmacology 100:477–484
Kurosawa M, Sato A, Sato Y (1989) Well-maintained responses of acetylcholine release and blood flow in the cerebral cortex to focal electrical stimulation of the nucleus basalis of Meynert in aged rats. Neurosci Lett 100:198–202
Light LL (1991) Memory and aging: four hypotheses in search of data. Annu Rev Psychol 42:333–376
Ljungberg T, Enquist M (1987) Disruptive effects of low doses ofd-amphetamine on the ability of rats to organize behaviour into functional sequences. Psychopharmacology 93:146–151
Mackworth NH (1957) Some factors affecting vigilance. Adv Sci 53:389–393
Madden DJ, Allen PA (1991) Adult age differences in the rat of information extraction during visual search. J Gerontol 46:P124-P126
Martin JV, Cook JM, Hagen TJ, Mendelson WB (1989) Inhibition of sleep and benzodiazepine receptor binding by aβ-carboline derivative. Pharmacol Biochem Behav 34:37–42
Moore H, Dudchenko P, Bruno JP, Sarter M (1992a) Toward modeling age-related changes of attentional abilities in rats: simple and choice reaction time tasks and vigilance. Neurobiol Aging 13:759–772
Moore H, Sarter M, Bruno JP (1992b) Age-dependent modulation of in vivo cortical acetylcholine release by benzodiazepine receptor ligands. Brain Res 596:17–29
Moore H, Sarter M, Bruno JP (1993a) Bidirectional modulation of stimulated cortical acetylcholine release by benzodiazepine receptor ligands. Brain Res 596:17–29
Moore H, Sarter M, Bruno JP (1993b) Modulation of stimulated cortical acetylcholine efflux by benzodiazepine receptor ligands is mediated in the basal forebrain. Soc Neurosci Abstr 19:128.12
Neils J, Newman CW, Hill M, Weiler E (1991) The effects of rate, sequencing, and memory on auditory processing in the elderly. J Gerontol 46:P71-P75
Nikaido AM, Ellinwood EH, Heatherly DG, Gupta SK (1990) Agerelated increase in CNS sensitivity to benzodiazepines as assessed by task difficulty. Psychopharmacology 100:90–97
Panikar KS, McNaughton N (1991) Comparison of the effects of buspirone and chloridazepoxide on successive discrimination. Pharmacol Biochem Behav 39:275–278
Parasuraman R (1979) Memory load and event-rate control sensitivity decrements in sustained attention. Science 205:924–927
Parasuraman R (1991) Attention and driving skills in aging and Alzheimer's disease. Hum Fact 33:539–557
Parasuraman R, Giambra L (1991) Skill development in vigilance: effects of event-rate and age. Psychol Aging 6:155–169
Parasuraman R Nestor PG (1991) Attention and driving skills in aging and Alzheimer's disease. Hum Fact 33:539–557
Parasuraman R, Warm JS, Dember WN (1987) Vigilance: taxonomy and utility. In: Mark LS, Warm JS, Huston RL (eds) Ergonomics and human factors. Springer, New York, pp 11–32
Parasuraman R, Greenwood PM, Haxby JV, Grady CL (1992) Visuospatial attention in dementia of the Alzheimer type. Brain 115:711–733
Perry EK, Johnson M, Kerwin JM, Piggott MA, Court JA, Shaw PJ, Ince PG, Brown A, Perry RH (1992) Convergent cholinergic activities in aging and Alzheimer's disease. Neurobiol Aging 13:393–400
Pomara N, Stanley B, Block R, Guido J, Russ D, Berchou R, Stanley M, Greenblatt DJ, Newton RE, Gershon S (1984) Adverse effects of single therapeutic doses of diazepam on performance in normal geriatric subjects: relationship to plasma concentration. Psychopharmacology 84:342–346
Pomara N, Deptula D, Medel M, Block RI, Greenblatt D (1989) Effects of diazepam on recall memory: relationship to aging, dose, and duration of treatment. Psychopharmacol Bull 25:144–148
Preston GC, Broks P, Traub M, Ward P, Poppleton P, Stahl SM (1988) Effects of lorazepam on memory, attention and sedation in man. Psychopharmacology 95:208–215
Reidenberg MM, Levy M, Warner H, Coutinho CB, Schwartz MA, Yu G, Cheripko J (1978) Relationship between diazepam dose, plasma level, age, and central nervous system depression. Clin Pharmacol Ther 23:371–374
Rich JB, Brown GG (1992) Selective dissociations of sedation and amnesia following ingestion of diazepam. Psychopharmacology 106:346–350
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
Roy-Byrne PP, Uhde TW, Holcomb H, Thompson K, King AK, Weingartner H (1987) Effects of diazepam on cognitive processes in normal subjects. Psychopharmacology 91:30–33
Sahakian BJ, Downes JJ, Eagger S, Evenden JL, Levy R, Philpot MP, Roberts AC, Robbins TW (1990) Sparing of attentional relative to mnemonic function in a subgroup of patients with dementia of the Alzheimer type. Neuropsychology 11:1197–1213
Sahgal A (1987) Some limitations of indices derived from signal detection theory: evaluation of an alternative index for measuring bias in memory tasks. Psychopharmacology 91:517–520
Sahgal A (1989) Vasopressin and amphetamine, but not desglycinamide vasopressin, impair positively reinforced visual attention performance in rats. Behav Brain Res 29:35–42
Sarter M, Bodewitz G, Stephens DN (1988) Attenuation of scopolamine-induced impairment of spontaneous alternation behavior by antagonist but not inverse agonist and agonist β-carbolines. Psychopharmacology 94:491–495
Sarter M (1994) Neuronal mechanisms of the attentional dysfunctions in senile dementia and schizophrenia: two sides of the same coin? Psychopharmacology 114:539–550
Sarter M, Bruno JP (1994) Cognitive functions of cortical acetylcholine: lessons from studies on the transsynaptic modulation of activated efflux. Trends Neurosci 17:217–221
Sarter M, Steckler T (1989) Spontaneous exploration of a 6-arm radial tunnel maze by basal forebrain lesioned rats: effects of the benzodiazepine receptor antagonistβ-carboline ZK 93426. Psychopharmacology 98:193–202
Sarter M, Bruno JP, Dudchenko P (1990) Activating the damaged basal forebrain cholinergic system: tonic stimulation versus signal amplification. Psychopharmacology 101:1–17.
Sarter M, Dudchenko P, Moore H, Holley LA, Bruno JP (1992) Cognition enhancement based on GABA-cholinergic interactions. In: Levin ED, Decker M, Butcher LL (eds) Neurotransmitter interactions and cognitive function. Birkhauser, Boston, pp 329–354
Sarter M, McGaughy J, Holley LA, Dudchenko P (1994) Behavioral facilitation and cognition enhancement. In Sarter M, Nutt D, Lister R (eds) Benzodiazepine receptor inverse agonists. John Wiley, New York pp 213–242
Scerbo MW, Warm JS, Doettling VS, Parasuraman R, Fisk AD (1987) Event asynchrony and task demands in sustained attention. In: Mark LS, Warm JS, Huston RL (eds) Ergonomics and human factors: recent research. Springer, New York, pp 33–39
Shannon HE, Guzman F, Cook JM (1984)β-Carboline-3-carboxylate-t-butyl ester: a selective BZ1 benzodiazepine receptor antagonist. Life Sci 35:2227–2236
Sharpe MH (1992) Auditory attention in early Parkinson's disease: an impairment in focused attention. Neuropsychology 30:101–106
Stephens DN, Sarter M (1988) Bidirectional nature of benzodiazepine receptor ligands extends to effects on vigilance. In: Hindmarch I, Ott H (eds) Benzodiazepine receptor ligands, memory and information processing. Springer, Berlin, pp 205–217
Sunderland T, Weingartner H, Cohen RM, Tariot PN, Newhouse PA, Thompson KE, Lawlor BA, Mueller EA (1989) Low-dose oral lorazepam administration in Alzheimer subjects and agematched controls. Psychopharmacology 99:129–133
Wickens CD (1984) Engineering psychology and human performance. Harper Collins, Columbus, Ohio
Zar JH (1974) Biostatistical analysis. Prentice Hall, N.J.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
McGaughy, J., Sarter, M. Behavioral vigilance in rats: task validation and effects of age, amphetamine, and benzodiazepine receptor ligands. Psychopharmacology 117, 340–357 (1995). https://doi.org/10.1007/BF02246109
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF02246109