Abstract
Two major difficulties confront ethopharmacological investigations on cognitive abilities such as social recognition in drug-treated animals involved in free social interactions. The first concerns the choice of the most relevant behaviours, those reflecting the cognitive abilities attributed to the animals and assessing the specificity of the drug activity, and those reflecting non-specific drug effects. The second refers to the experimenter's awareness that in contrast to physical objects, social stimuli respond to drug-treated subjects and that their own level of responsiveness may influence the changes of drug-treated subjects' social interest. In addition, their contribution may vary according to the different treatments the drug-treated subjects receive. In examining the effects of tetrahydroaminoacridine (THA) at doses of 0.3, 1 and 3 mg/kg on the ability of adult male rats to recognize previously encountered conspecifics, we attempted to take into consideration such difficulties. A detailed behavioural profile of drug-treated rats was reported to separate specific from non-specific effects of THA. In addition, rats were assigned an index of responsibility for contact which takes into account the interactive dimension of each dyad and allows relevant comparisons between different treatments. The doses of THA which were found to decrease the duration of exploration of a familiar juvenile were also found to decrease the number of contacts initiated by the drug-treated subjects. THA induced a relative increase in body care by comparison to saline treatment. However, it had no effect of locomotor activity and rearing of the subjects. These findings enable dissociation of the effects of THA on cognitive versus non-cognitive processes.
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References
Bartus RT, Dean RL, Beer B (1983) An evaluation of drugs for improving memory in aged monkeys: implications for clinical trials in humans. Psychopharmacol Bull 19:168–184
Bluthé RM, Dantzer R (1990) Social memory does not involve vasopressinergic neurotransmission in female rats. Brain Res 535:301–304
Bluthé RM, Dantzer R (1992) Chronic intracerebral infusions of vasopressin and vasopressin antagonist modulate social recognition in rat. Brain Res 572:261–264
Bluthé RM, Dantzer R (1993) Role of the vomeronasal system in vasopressinergic modulation of social recognition in rats. Brain Res 604:205–210
Bluthé RM, Schoenen J, Dantzer R (1990) Androgen-dependent vasopressinergic neurons are involved in social recognition in rats. Brain Res 519:150–157
Conover WJ (1980) Practical nonparametric statistics, 2nd ed. Wiley, New York
Dantzer R, Bluthé RM (1992) Vasopressin involvement in antipyresis, social communication, and social communication: a synthesis. Crit Rev Neurobiol 16:243–255
Dantzer R, Bluthé RM, Koob GF, LeMoal M (1987) Modulation of social memory in male rats by neurohypohyseal peptides. Psychopharmacology 91:363–368
Dantzer R, Koob GF, Bluthé RM, LeMoal M (1988) Septal vasopressin modulates social memory in male rats. Brain Res 519:150–157
Dawson GR, Heyes CM, Iversen SD (1992) Pharmacological mechanisms and animal models of cognition. Behav Pharmacol 3:285–297
Delius JD (1970) Irrelevant behaviour, information processing and arousal homeostasis. Psychol Forsch 33:165–188
Dixon AK, Fisch HU, McAllister KH (1990) Ethopharmacology: a biological approach to the study of drug-induced changes in behavior. Adv Stud Behav 19:171–204
Drukarch B, Kits KS, Van der Meer EG, Lodder JC, Stoof JC (1987) 9-Amino-1,2,3,4,-tetrahydroaminoacridine (THA) an alleged drug for the treatment of Alzheimer's disease inhibits acetylcholinesterase activity and outward K+ current. Eur J Pharmacol 141:153–157
Fitten LJ, Flood JF, Baxter CF, Tachiki KH, Perryman K (1987) Long-term oral administration of memory-enhancing doses of tacrine in mice: a study of potential toxicity and side effects. J. Gerontol 42:681–685
Fitten LJ, Perryman K, Tachiki KH, Ling A (1988) Oral tacrine administration in middle-aged monkeys: effects on discrimination learning. Neurobiol Aging 9:221–224
Flood JF, Smith GE, Cherkin A (1985) Memory enhancement: supra-additive effect of subcutaneous cholinergic drug combinations in mice. Psychopharmacology 86:61–67
Freeman SE, Dawson RM (1991) Tacrine: a pharmacological review. Prog Neurobiol 36:257–277
Gao B, Culter MG (1992a) Effects of acute administration of the 5-HT3 receptor antagonist, BRL 46470A, on the behaviour of mice in a two compartment light-dark box and during social interaction in their home cage and an unfamiliar neutral cage. Neuropharmacology 31:743–748
Gao B, Cutler MG (1992b) Effects of acute and subchronic administration of propanolol on the social behaviour of mice: an ethopharmacological study. Neuropharmacology 31:749–756
Gipsen WH, Issacson RL (1981) ACTH-induced excessive grooming in the rat. Pharmacol Ther 12:209–246
Harriman AE, Thiessen DD (1985) Harderian letdown in male Mongolian gerbils (Meriones unguiculatus) contributes to proceptive behavior. Horm Behav 19:213–219
Hodges H, Ribeiro AM, Gray JA, Martchbanks RM (1990) Low dose tetrahydroaminoacridine (THA) improves cognitive function but does not affect brain acetylcholine in rats. Pharmacol Biochem Behav 36:291–298
Irvin RW, Szot P, Dorsa DM, Potegal M, Ferris CF (1990) Vasopressin in the septal area of the golden hamster controls scent marking and grooming. Physiol Behav 48:693–699
Kaye WH, Stiaram N, Weingartner H, Ebert MH, Smallberg S, Gillin JC (1982) Modest facilitation of memory in dementia with combined lecithin and anticholinesterase treatment. Biol Psychiatry 17:275–280
Kumar V (1988) Efficacy and side effects of THA in Alzheimer's disease patients. In: Giacobini E, Becker R (eds) Current research in Alzheimer therapy. Taylor and Francis, New York, pp 225–229
Martin P, Bateson PPG (1986) Measuring behaviour. An introductory guide. Cambridge University Press, Cambridge
Miczek KA (1983) Ethopharmacology. Alan R. Liss, New York
Mitchell PJ, Redfern PH (1992) Acute and chronic antidepressant drug treatments induce opposite effects in the social behaviour of rats. J Psychopharmacol 6:241–257
Nordberg A, Nilsson-Hakansson L, Adem A, Lai Z, Winblad B (1989) Multiple actions of THA on cholinergic neurotransmission in Alzheimer brains. Prog Clin Biol Res 317:1169–1178
Osterrieder W (1987) 9-Amino-1,2,3,4,-tetrahydroaminoacridine (THA) is a potent blocker of cardiac potassium channels. Br J Pharmacol 92:521–526
Pério A, Terranova JP, Worms P, Bluthé RM, Dantzer, R, Biziére K (1989) Specific modulation of social memory in rats by cholinomimetic and nootropic drugs, by benzodiazepine inverse agonists, but not by psychostimulants. Psychopharmacology 97:262–268
Perry EK, Smith CJ, Court JA, Bonham JR, Rodway M, Atack JR (1988) Interaction of 9-amino-1,2,3,4,-tetrahydroaminoacridine (THA) with human cortical nicotinic and muscarinic receptor binding in vitro. Neurosci Lett 91:211–216
Roberts WM, Bergquist EH, Robinson TCL (1969) Thermoregulatory grooming and sleep-like relaxation induced by local warming of preoptic area and anterior hypothalamus in opposum. J. Comp Physiol Psychol 87:182–188
Sekigushi R, Wolterink G, Van Ree JM (1991) Short duration of retroactive facilitation of social recognition in rats. Physiol Behav 50:1253–1256
Shaw FH, Bentley GA (1953) The pharmacology of some new anticholinesterases. Aust J Exp Biol Med Sci 31:573–576
Stevens DR, Cotman CW (1987) Excitatory actions of tetrahydro-9-aminoacridine (THA) on hippocampus pyramidal neurons. Neurosci Lett 79:301–305
Summers WK, Viesselman JO, Marsh GM, Candelora K (1981) Use of THA in treatment of Alzheimer-like dementia: pilot study in twelve patients. Biol Psychiatry 16:145–153
Summers WK, Majowski LV, Marsh GM, Tachiki K, Kling A (1986) Oral tetrahydroaminoacridine in long-term treatment of senile dementia, Alzheimer's type. N Engl J Med 315: 1241–1245
Tachiki KH, Spidell K, Samuels L, Ritzmann R, Steinberge A, Lloyd RL, Summers WK, Kling A (1988) Tacrine: levels and effects on biogenic amines and their metabolites in specific areas of the rat brain. In: Giacobini E, Becker R (eds) Current research in Alzheimer therapy. Taylor and Francis, New York, pp 217–221
Tanaka H, Kanosue K, Nakayama T, Shen Z (1986) Grooming, body extension and vasomotor responses induced by hypothalamic warming at different body temperatures. Physiol Behav 38:145–151
Thiessen DD (1988) Body temperature and grooming in the Mongolian gerbil. Ann NY Acad Sci 525:27–39
Thiessen DD, Pendergrass M, Young RK (1983) Development and expression of autogrooming in the Mongolian gerbil,Meriones unguiculatus. J Comp Psychol 97:190–197
Thor DH, Holloway WR (1982) Social memory of the male rats. J. Comp Physiol Psychol 96:1000–1006
Weintraub M, Standish R (1988) Tetrahydroaminoacridine: a possible treatment for senile dementia of the Alzheimer type. Hosp Form 23:31–35
Worms P, Kan JP, Steinberg R, Terranova JP, Pério A, Biziére K (1989) Cholinomimetic activities of minaprine. Naunyn-Schmiedeberg's Arch Pharmacol 340:411–418
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Gheusi, G., Bluthe, RM., Goodall, G. et al. Ethological study of the effects of tetrahydroaminoacridine (THA) on social recognition in rats. Psychopharmacology 114, 644–650 (1994). https://doi.org/10.1007/BF02244996
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DOI: https://doi.org/10.1007/BF02244996