The present study investigated the role of 5-HT1A and 5-HT2 receptors in the execution of a working memory task (delayed non-matching to position, DNMTP) by assessing the influence of 8-OH-DPAT (5-HT1A receptor agonist) and DOI (5-HT 2 receptor agonist) on the performance of rats lesioned with 5,7-dihydroxytryptamine (5,7-DHT) and their controls. Post-mortem neurochemical analysis revealed that serotonin and 5-hydroxyindoleacetic acid levels were reduced in examined brain areas (especially in the hippocampus where there was a 90 percent reduction). Noradrenaline concentrations were also decreased (mostly on the same side of the injection) by about 20 percent. 5,7-DHT lesioned rats did not significantly differ from their controls in performance in the DNMTP task. At the 30 μg/kg dose, 8-OH-DPAT did not affect the DNMTP-performance of rats, but at the higher dose (100 μg/kg) it reduced the probability of responding to the sample lever. DOI (100 and 300 μg/kg) also interfered with the non-cognitive performance of rats. Since neither of these agonists affected significantly the choice accuracy, they do not appear to influence the working memory per se. The 5,7-DHT lesioned rats did not differ from their controls in response to these agonists.
These results suggest that the combination of 5-HT1A receptor stimulation by 8-OH-DPAT and 5-HT2 receptor stimulation by DOI can interfere with the non-cognitive performance of rats in the DNMTP task. The results further indicate that the effect of 8-OH-DPAT may be mediated through post-synaptic rather than pre-synaptic 5-HT1A receptors.
Aggleton J.P., Neave N., Nagle S., Sahgal A. (1995) A comparison of the effects of medial prefrontal, cingulate cortex and cingulum bundle lesions on tests of spatial memory: evidence of a double dissociation between frontal and cingulum bundle contributions . J Neurosci15: 7270-7281
2.
Altman H.J., Normile H.J. (1988) What is the nature of the role of serotonergic system in learning and memory: prospects for the development of an effective treatment strategy for senile dementia. Neurobiol Aging9: 627-638
3.
Arora R.C., Meltzer H.Y. (1989) Increased serotonin2 (5-HT2) receptor binding as measured by 3H-lysergic acid diethylamide ( 3H-LSD) in the blood platelets of depressed patients. Life Sci44: 725-734
4.
Biegon A., Grinspoon A., Blumenfeld B., Bleich A., Apter A., Mester R. (1990a) Increased serotonin 5-HT2 receptor binding on blood platelets of suicidal men. Psychopharmacology , Berlin100: 165-167
5.
Biegon A., Essar N., Israeli M., Elizur A., Bruch S., Bar-Nathan A.A. (1990b) Serotonin 5-HT2 receptor binding on blood platelets as a state dependent marker in major affective disorder. Psychopharmacology, Berlin102: 73-75
6.
Boess FG, Martin I.L. (1994) Review: Molecular biology of 5-HT receptors. Neuropharmacology33: 275-317
7.
Carli M., Samanin R. (1992a) Serotonin2 receptor agonists and serotonergic anorectic drugs affect rats' performance differently in a five-choice serial reaction time task. Psychopharmacology106: 228-234
8.
Carli M., Samanin R. (1992b) 8-Hydroxy-2-(di-n-propylamino)tetralin impairs spatial learning in a water maze: role of post-synaptic 5-HT1A receptors. Br J Pharmac105: 720-726
9.
Carli M., Tranchina S., Samanin R. (1992a) 8-Hydroxy-2-(di-n-propyl-amino)tetralin, a 5-HT 1A receptor agonist, impairs performance in a passive avoidance task . Eur J Pharmac211: 227-234
10.
Carli M., Lazarova M., Tatarczynska E., Samanin R. (1992b) Stimulation of 5-HT1A receptors in the dorsal hippocampus impairs acquisition and performance of a spatial task in a water maze. Brain Res595: 50-56
11.
Cassel J-C., Jeltsch H. (1995) Serotonergic modulation of cholinergic function in the central nervous system: cognitive implications. Neuroscience69:1-41
12.
Cole BJ, Jones GH, Turner JD (1994) 5-HT1A receptor agonists improve the performance of normal and scopolamine-impaired rats in an operant delayed matching to position task. Psychopharmacology116: 135-142
13.
Cross A.J. (1990) Serotonin in Alzheimer-type dementia and other dementing illnesses. In Whitaker-Azmitia PM , Peroutka S J (eds), The neuropharmacology of serotonin, Vol. 600. Annals of the New York Academy of Science, pp. 405-417
14.
Deacon R M J (1991) Pharmacological studies of a rat spatial delayed nonmatch-to-sample task as an animal model of dementia. Drug Dev Res24: 67-79
15.
Decker M.W., McGaugh J.L. (1991) The role of interactions between the cholinergic system and other neuromodulatory systems in learning and memory. Synapse7: 151-168
16.
Dourish C.T., Hutson P.H., Curzon G. (1985) Low doses of the putative serotonin agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) elicit feeding in the rat. Psychopharmacology86:197-204
17.
Dudchenko P., Sarter M. (1992) Behavioral microanalysis of spatial delayed alternation performance: rehearsal through overt behavior, and effects scopolamine and chlordiazepoxide. Psychopharmacology107: 263-270
18.
Dunnett S.B. (1990) Role of prefrontal cortex and striatal output systems in short-term memory deficits associated with ageing, basal forebrain lesions and cholinergic-rich grafts. Can J Psychol44: 210-232
19.
Dunnett S.B. (1993) Operant delayed matching and non-matching to position in rats. In Sahgal A (eds), Behavioral neuroscience, a practical approach, Vol. I, Oxford University Press, Oxford pp. 123-136
Dobrossy M.D., Svendsen C.N., Dunnett S.B. (1995) The effects of bilateral striatal lesions on the acquisition of an operant test of short term memory. NeuroReport6: 2049-2053
22.
Fletcher PJ (1987) 8-OH-DPAT elicits gnawing, and eating of solid but not liquid foods. Psychopharmacology92:192-195
23.
Fletcher PJ, Zack M.H., Coscina DV (1991) Influence of taste and food texture on the feeding responses induced by 8-OH-DPAT and gepirone. Psychopharmacology104: 302-306
24.
Griebel G. (1995) 5-Hydroxytryptamine-interacting drugs in animal models of anxiety disorders: more than 30 years of research. Pharmac Ther65: 319-395
25.
Hoyer D., Clarke DE, Fozard J.R., Hartig P.R., Martin G.R., Mylecharane E.J., Saxena P.R., Humphrey P PA (1994) VIIth International union of pharmacology classification of receptors for 5-hydroxytryptamine (serotonin). Pharmac Rev46:157-203
26.
Hurlbut K.M. (1991) Drug-induced psychoses. Emer Med Clin N Am9: 31-52
27.
Jansen J H M, Andrews J.S. (1994) The effects of serotonergic drugs on short-term spatial memory in rats. J Psychopharmac8:157-163
28.
Joyce J.N., Shane A., Lexow N., Winokur A., Casanova M.F., Kleinman J.E. (1993) Serotonin uptake sites and serotonin receptors are altered in the limbic system of schizophrenics. Neuropsychopharmacology8: 315-336
29.
Jäkala P., Sirviö J., Riekkinen P. Jr, Riekkinen P. (1993) Effects of p-chlorophenylalanine and methysergide on the performance of a working memory task. Pharmac Biochem Behav44: 411-418
30.
Jäkala P., Sirvio J., Koivisto E., Bjorklund M., Kaukua J., Riekkinen P. Jr (1995) Modulation of rat neocortical high-voltage spindle activity by 5-HT1/5-HT2 receptor subtype specific drugs . Eur J Pharmac282: 39-55
31.
Kitchener S.J., Dourish C.T. (1994) An examination of the behavioral specificity of hypophagia induced by 5-HT1B, 5-HT1C and 5-HT2 receptor agonists using the post-prandial satiety sequence in rats . Psychopharmacology, Berlin113: 369-377
32.
Leikin J.B., Krantz A.J., Zell-Kanter M., Barkin R.L., Hryhorczuk D.O. (1989) Clinical features and management of intoxication due to hallucinogenic drugs. Med Toxicol Adverse Drug Exp4: 324-350
33.
Leysen J.E., Pauwels PJ (1990) Central and peripheral 5-HT2 receptors : role in physiological versus pathological conditions. In Proceedings of the symposium on serotonin from cell biology to pharmacology and therapeutics. Kluwer, Amsterdam pp. 323-329
34.
Lucki I. (1992) 5-HT1 receptors and behavior. Neurosci Biobehav Rev16: 83-93
35.
Martin G.R., Humphrey P PA (1994) Classification review: receptors for 5-hydroxytryptamine: current perspectives on classification and nomenclature. Neuropharmacology33: 261-273
36.
Mefford I.N. (1981) Application of high performance liquid chromatography with electrochemical detection to neurochemical analysis: measurements of catecholamines, serotonin and metabolites in rats brain. J Neurosci Methods3: 310-338
37.
Morilak DA, Ciaranello RD (1993) 5-HT2 receptor immunoreactivity on cholinergic neurons of the pontomesencephalic tegmentum shown by double immunofluorescence . Brain Res627: 49-54
38.
Morilak D.A., Garlow S.J., Ciaranello R.D. (1993) Immunocytochemical localization and description of neurons expressing serotonin2 receptors in the rat brain. Neuroscience54: 701-717
39.
Palmer AM, Stratmann MA, Procter A.W., Bowen DM (1988) Possible neurotransmitter basis of behavioral changes in Alzheimer's disease. Ann Neurol23: 616-620
40.
Pandey G.N., Pandey S.C., Janicak P.G., Marks R.C., Davis J.M. (1990) Platelet serotonin-2 receptor binding sites in depression and suicide. Biol Psychiat28: 215-222
41.
Pontecorvo M.J., Sahgal A., Steckler T. (1996) Further developments in the measurement of working memory in rodents. Cogn Brain Res3: 205-213
42.
Puumala T., Sirvio J. (1997) Stimulation and blockade of α1 adrenoceptors affect behavioural activity, but not spatial working memory assessed by delayed non-matching to position task in rats. J Psychopharmac11: 51-57
43.
Riekkinen P. Jr (1994) 5-HT1A and muscarinic acetylcholine receptors jointly regulate passive avoidance behavior. Eur J Pharmac262: 77-90
44.
Ruotsalainen S., Sirviö J., Jakala P., Puumala T., MacDonald E., Riekkinen P. Sr (1997) Differential effects of three 5-HT receptor antagonists on the performance of rats in attentional and working memory tasks . Eur Neuropsychopharmac in press
45.
Ruotsalainen S., (1997) Serotonergic system and its interactions with cholinergic receptor mediated mechanisms in the modulation of working memory, an experimental study. Series of Reports, Department of Neurology, No. 43, University of Kuopio
46.
Sahgal A., Keith A.B. (1993) Combined serotonergic-cholinergic lesions do not disrupt memory in rats. Pharmac Biochem Behav45: 995-1001
47.
Sanders-Bush E. (1990) Adaptive regulation of central serotonin receptors linked to phosphoinositide hydrolysis. Neuropsychopharmacology3: 411-416
48.
Sirvio J., Riekkinen P. Jr, Jakala P., Riekkinen P.J. (1994) Experimental studies on the role of serotonin in cognition. Prog Neurobiol43: 363-379
49.
Stanhope KJ, McLenachan A.P., Dourish C.T. (1995) Dissociation between cognitive and motor/motivational deficits in the delayed matching to position test: effects of scopolamine, 8-OH-DPAT and EAA antagonists. Psychopharmacology122: 268-280
50.
Steckler T., Sahgal A. (1995) The role of serotonergic-cholinergic interactions in the mediation of cognitive behaviour. Behav Brain Res67:165-199
51.
Vanderwolf C.H., Baker G.B., Dickson C. (1990) Serotonergic control of cerebral activity and behavior: models of dementia. In Whitaker-Azmitia PM , Peroutka SJ (eds), The neuropharmacology of serotonin, Vol. 600. Annals of New York Academy of Science, pp. 366-383
52.
Warburton E.C., Harrison A.A., Robbins T.W., Everitt B.J. (1997) Contrasting effects of systemic and intracerebral infusions of the 5-HT1A receptor agonist 8-OH-DPAT on spatial short-term working memory in rats. Behav Brain Res84: 247-258
