,, : Current Status in Drug Addiction and Addiction Memory Research WAN G Hao2Ran 1, GAO Xiang2 Rong 1, ZHAN G Kai2Gao 2, HAN Ji2Sheng 1 ( 1
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1 ( ) : R Current Status in Drug Addiction and Addiction Memory Research WAN G Hao2Ran 1 GAO Xiang2 Rong 1 ZHAN G Kai2Gao 2 HAN Ji2Sheng 1 ( 1 D rug Dependence Peki ng U niversity Beijing ) Neuroscience Research Instit ute 2 N ational Instit ute on Abstract The central feature of drug addiction is compulsive drug use loss of control over appar2 ently voluntary acts of drug seeking and drug taking. Drug addiction as a chronic brain disease may result f rom abnormal engagement of long2term associative memory. Addiction and memory are likely to share much in common in t he aspect s of neural adaptations synaptic plasticity and related molecular mechanisms. This paper reviews t he possible roles of learning mechanisms in t he develop ment of re2 lapse sensitization and drug addiction abnormal associative learning and compulsive behavior addic2 tion memory and addiction multiple memory systems and the development of addiction and empha2 size t he importance of synaptic plasticity and addiction memory in drug addiction. Addiction is charac2 terized by t he involvement of specific learning patterns of information. Addiction is closely related to t he disorder of associate learning t hat depends on dopamine. Hippocampus may play a key role in ad2 diction. At last we put forward the future directions for research. Key words Addiction memory Drug addiction Associate learning Neural circuits Molecular mech2 anisms : [13 ] CA1 ( V TA) addiction memory [4 5 ] aberrant memory [1 ] (L TP) [ : (L TD) ] V TA CA1 L TP ( ) : D1 (camp/ P KA/ CREB)
2 ( ) ( ) 2 2 [15 ] 2 (1) ( ) 1 2 D1 :D1 :D2 :D2 GPi/ SNr : / GPe : SNc/ V TA : / ( 1) L TP L TD [5 ] : [1 ] ( ) L TP 2 (AMPA) D1 D2 N2 2D2 ( NM2 DA) [2 ] AMPA AMPA [1 3 8 ] [9 ] [15 ] Nestler Total Recall the Memory of Addiction [5 ] : (1) [13 ] (2) [2 3 ] (3) camp/ P KA/ CREB [13 ] (4 ) camp (CREB) [13 ] (5) [1 2 ] (6) [2 3 ]
3 ( [9 ] ) [1 8 ] (psychostimulant s) [1 8 ] [13 ] D1 [14 ] [14 ] [8 ] ( ) ( non2associative sensitization) [10 ] CA1 [11 ] / [1 8 Alan Leshner ] : (laying down of memory trace) [12 ] [1 3 ] 2 [1 ] [1 3 ] [15 ]
4 [13 ] 2 ( multiple memory systems) [13 16 ] : [18 ] 2 (memory of addiction) 1972 Mello [17 ] [1 17 ] : 2 [4 ] : (1) (2) [4 ] 1 [1 19 ] (cross2sensitization) [1 5 ] : (1) (2) FosB CREB (3) (4)
5 ( 19) ( ) : ( ) ( ) : 2 gene expression of acute and chronic morphine dependent neural cells. Chinese J Neurosci 2001 Supplement. O : 10 Vorel SR Liu X Hayes RJ et al. Relapse to cocaine2 seeking after hippocampal theta burst stimulation. Sci2 ence g Pu L Bao GB Xu NJ et al. Hippocampal long2term po2 1 Berke JD Hyman SE. Addiction dopamine and the molecular mechanisms of memory. Neuron g Nestler EJ. Molecular basis of long2term plasticity underly2 ing addiction. Nat Rev Neurosci g Hyman SE Hyman SE Malenka RC. Addiction and the brain: the neurobiology of compulsion and its persistence. Nat Rev Neurosci g Boening JA. Neurobiology of an addiction memory. J Neu2 ral Transm g Nestler EJ. Neurobiology. Total recal the memory of addiction. Science g Sutton MA Schmidt EF Choi KH et al. Extinction2in2 duced upregulation in AMPA receptors reduces cocaine2seek2 ing behaviour. Nature g Thompson AM Gosnell BA Wagner JJ. Enhancement of long2term potentiation in the rat hippocampus following co2 caine exposure Neuropharmacology g Di CG. Drug addiction as dopamine2dependent associative learning disorder. Eur J Pharmacol g Wang HR( ) Gao XR ( ) Han Ji2Sheng ( ) et al. DD2PCR and DNA microarray analysis of tentiation is reduced by chronic opiate treatment and can be restored by re2exposure to opiates. J Neurosci g Holden C. Drug addiction. Zapping memory center trig2 gers drug craving. Science g Vezina P Steward J. Amphetamine administered to the ventral tegmental area but not to the nucleus accumbens sensitizes rats to systemic morphine : lack of conditioned effects. Brain Res g Robinson TE Berridge KC. The neural basis of drug craving: an incentive2sensitization theory of addiction. Brain Res g Di CG. A motivational learning hypothesis of the role of mesolimbic dopamine in compulsive drug abuse. J chopharmacol g5467. Psy2 16 Harlan RE Garcia MM. Drugs of abuse and immediate2 early genes in the fore brain. Mol Neurobiol g Heyyne A May T Goll P. Wolffgramm J. Persisting consequences of drug intake : towards a memory of addic2 tion. J Neural Transm g Milner B Squire L R Kandel ER. Cognitive neuroscience and the study of memory. Neuron g White NM. Addictive drugs as reinforcers : multiple partial actions on memory systems. Addiction g
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