Caffeine reverses age-related deficits in olfactory discrimination and social recognition memory in rats Involvement of adenosine A1 and A2A receptors

Caffeine, a non-selective adenosine receptor antagonist, has been suggested as a potential drug to counteract age-related cognitive decline since critical changes in adenosinergic neurotransmission occur with aging. In the present study, olfactory discrimination and short-term social memory of 3, 6, 12 and 18 month-old rats were assessed with the olfactory discrimination and social recognition tasks, respectively. The actions of caffeine (3.0, 10.0 and 30.0 mg/kg, i.p.), the A1 receptor antagonist DPCPX (1.0 and 3.0 mg/kg, i.p.) and the A2A receptor antagonist ZM241385 (0.5 and 1.0 mg/kg, i.p.) in relation to age-related effects on olfactory functions were also studied. The 12 and 18 month-old rats exhibited significantly impaired performance in both models, demonstrating deficits in their odor discrimination and in their ability to recognize a juvenile rat after a short period of time. Acute treatment with caffeine or ZM241385, but not with DPCPX, reversed these age-related olfactory deficits. The present results suggest the participation of adenosine receptors in the control of olfactory functions and confirm the potential of caffeine for the treatment of aged-related cognitive decline.

[1]  H. Praag,et al.  Caffeine attenuates scopolamine-induced memory impairment in humans , 2005, Psychopharmacology.

[2]  Dean A. Pollina,et al.  Amnesia Associated with Electroconvulsive Therapy , 1997 .

[3]  G D Pearlson,et al.  Olfactory recognition: differential impairments in early and late Huntington's and Alzheimer's diseases. , 1987, Journal of clinical and experimental neuropsychology.

[4]  E. Barrett-Connor,et al.  Coffee consumption and cognitive function among older adults. , 2002, American journal of epidemiology.

[5]  Y. Lamberty,et al.  Scopolamine effects on juvenile conspecific recognition in rats: Possible interaction with olfactory sensitivity , 1988, Behavioural Processes.

[6]  E. Miyoshi,et al.  Facilitation of short-term social memory by ethanol in rats is mediated by dopaminergic receptors , 2004, Behavioural Brain Research.

[7]  F. Roman,et al.  Age-related learning and memory deficits in odor-reward association in rats , 1996, Neurobiology of Aging.

[8]  M. Jarvis,et al.  Does caffeine intake enhance absolute levels of cognitive performance? , 2005, Psychopharmacology.

[9]  H. Eichenbaum,et al.  Cognitive decline associated with normal aging in rats: a neuropsychological approach. , 1995, Learning & memory.

[10]  D. G. Hazzard.  Relevance of the rodent model to human aging studies , 1991, Neurobiology of Aging.

[11]  V. Cestari,et al.  Caffeine and cocaine interaction on memory consolidation in mice. , 1996, Archives internationales de pharmacodynamie et de therapie.

[12]  K. Tonosaki,et al.  Sensitivity of the olfactory sense declines with the aging in senescence-accelerated mouse (SAM-P1) , 2000, Physiology & Behavior.

[13]  B. Fredholm,et al.  International Union of Pharmacology. XXV. Nomenclature and classification of adenosine receptors. , 2001, Pharmacological reviews.

[14]  C. Da Cunha,et al.  The effect of caffeine in animal models of learning and memory. , 1999, European journal of pharmacology.

[15]  Geoffrey Schoenbaum,et al.  Teaching old rats new tricks: age-related impairments in olfactory reversal learning , 2002, Neurobiology of Aging.

[16]  R. Dantzer,et al.  Modulation of social memory in male rats by neurohypophyseal peptides , 1987, Psychopharmacology.

[17]  A. Gubitz,et al.  Tissue distribution of adenosine receptor mRNAs in the rat , 1996, British journal of pharmacology.

[18]  D. Souza,et al.  Neuroprotection by caffeine and adenosine A2A receptor blockade of β‐amyloid neurotoxicity , 2003, British journal of pharmacology.

[19]  M. Hadfield.  Caffeine and the olfactory bulb , 1997, Molecular Neurobiology.

[20]  R. Doty,et al.  Olfactory testing as an aid in the diagnosis of Parkinson's disease: development of optimal discrimination criteria. , 1995, Neurodegeneration : a journal for neurodegenerative disorders, neuroprotection, and neuroregeneration.

[21]  P. Soubrié,et al.  Social olfactory recognition in rodents: deterioration with age, cerebral ischaemia and septal lesion , 1994, Behavioural pharmacology.

[22]  E. Vizi,et al.  Age-dependent changes of presynaptic neuromodulation via A1-adenosine receptors in rat hippocampal slices fn2 fn2 [3H]-ACh, [3H]-acetylcholine; DPCPX, 8-cyclopentyl-1,3-dimethylxanthine; [H]-DPCPX, [3H]-8-cyclopentyl-1,3-dimethylxanthine; DPX, 1,3-diethyl-8-phenylxanthine; HPLC, high performance , 1997, International Journal of Developmental Neuroscience.

[23]  D. Weaver.  A2a adenosine receptor gene expression in developing rat brain. , 1993, Brain research. Molecular brain research.

[24]  Richard L. Doty,et al.  Presence of both odor identification and detection deficits in alzheimer's disease , 1987, Brain Research Bulletin.

[25]  J. Jolles,et al.  Cognition Enhancers in Age-Related Cognitive Decline , 1996, Drugs & aging.

[26]  W. Paré.  The effect of caffeine and seconal on a visual discrimination task. , 1961, Journal of comparative and physiological psychology.

[27]  R. Cunha,et al.  Adenosine as a neuromodulator and as a homeostatic regulator in the nervous system: different roles, different sources and different receptors , 2001, Neurochemistry International.

[28]  F. Angelatou,et al.  Reduction of A1 adenosine receptors in cortex, hippocampus and cerebellum in ageing mouse brain. , 1992, Neuroreport.

[29]  R. Cunha,et al.  Modification of A‐i and A2a adenosine receptor binding in aged striatum, hippocampus and cortex of the rat , 1995, Neuroreport.

[30]  R. Cooper,et al.  Vasopressin and conditioned flavor aversion in aged rats , 1980, Neurobiology of Aging.

[31]  S. Daniel,et al.  Commentary Qjm Is Parkinson's Disease a Primary Olfactory Disorder? , 2022 .

[32]  G. Rondouin,et al.  5-HT4 Receptors Improve Social Olfactory Memory in the Rat , 1997, Neuropharmacology.

[33]  R. Silveira,et al.  Caffeine reverses the memory disruption induced by intra-nigral MPTP-injection in rats , 2001, Brain Research Bulletin.

[34]  D P Salmon,et al.  Very Early Changes in Olfactory Functioning Due to Alzheimer's Disease and the Role of Apolipoprotein E in Olfaction a , 1998, Annals of the New York Academy of Sciences.

[35]  D. Dluzen,et al.  Age related changes of social memory/recognition in male fischer 344 rats , 1994, Behavioural Brain Research.

[36]  C. Murphy.  Loss of Olfactory Function in Dementing Disease , 1999, Physiology & Behavior.

[37]  J. Jolles,et al.  Habitual caffeine consumption and its relation to memory, attention, planning capacity and psychomotor performance across multiple age groups , 2000, Human psychopharmacology.

[38]  P. Coleman.  How old is old? , 1989, Neurobiology of Aging.

[39]  G. Taylor,et al.  Norepinephrine modulation of social memory: evidence for a time-dependent functional recovery of behavior. , 1995, Behavioral neuroscience.

[40]  B. Volpe,et al.  An animal model of human-type memory loss based on aging, lesion, forebrain ischemia, and drug studies with the rat , 1988, Neurobiology of Aging.

[41]  J. Ribeiro,et al.  Adenosine A2 receptor-mediated excitatory actions on the nervous system , 1996, Progress in Neurobiology.

[42]  J. Jolles,et al.  The effects of habitual caffeine use on cognitive change: a longitudinal perspective , 2003, Pharmacology Biochemistry and Behavior.

[43]  J. Burgunder,et al.  Expression of adenosine A2a receptors gene in the olfactory bulb and spinal cord of rat and mouse , 1999, Neuroscience Letters.

[44]  R. Prediger,et al.  Ethanol improves short-term social memory in rats. Involvement of opioid and muscarinic receptors. , 2003, European journal of pharmacology.

[45]  W. J. Carr,et al.  Olfactory recognition of conspecifics by domestic Norway rats. , 1976, Journal of comparative and physiological psychology.

[46]  R. Doty,et al.  Olfactory dysfunction in parkinsonism , 1988, Neurology.

[47]  R. Cunha,et al.  Increase in the Number, G Protein Coupling, and Efficiency of Facilitatory Adenosine A2A Receptors in the Limbic Cortex, but not Striatum, of Aged Rats , 1999, Journal of neurochemistry.

[48]  B. Turetsky,et al.  Olfactory Identification in Elderly Schizophrenia and Alzheimer’s Disease , 1997, Neurobiology of Aging.

[49]  Malcolm Lader,et al.  The influences of age and caffeine on psychomotor and cognitive function , 1999, Psychopharmacology.