Brain Research Reviews, 11 (1986) 157-198 157 Elsevier BRR 90048 Enduring Changes in Brain and Behavior Produced by Chronic Amphetamine Administration: A Review and Evaluation of Animal Models of Amphetamine Psychosis TERRY E. ROBINSON and JILL B. BECKER Department of Psychology and Neuroscience Laboratory Building, The University of Michigan, Ann Arbor, M148104-1687 (U.S.A.) (Accepted December 31st, 1985) Key words: amphetamine -- sensitization -- reverse tolerance -- dopamine -- catecholamine -- schizophrenia -- amphetamine psychosis -- animal model -- striatum-- stress-- sex difference -- conditioning-- neurotoxicity -- stereotypy -- autoreceptor CONTENTS 1. Introduction ............................................................................................................................................ 158 2. The effects of continuous amphetamine administration on brain and behavior (amphetamine neurotoxicity) ..................... 159 3. The behavioral consequences of repeated intermittent amphetamine administration (behavioral sensitization) ................. 160 3 1. The major characteristics of behavioral sensitization .................................................................................... 161 3.1.1. Behavior .................................................................................................................................. 161 3.1.2. Injection paradigm ..................................................................................................................... 163 3.1.3. Sex differences ........................................................................................................................... 163 3.1.4. Summary .................................................................. " ................................................................ 164 4. Behavioral sensitization and amphetamine neurotoxicity as animal models of amphetamine psychosis ............................. 164 5. The biological basis of behavioral sensitization .................................................................................................. 167 5 1. Drug dispositional/peripheral hypotheses .................................................................................................. 167 5_2 Drug-environment conditioning hypotheses ............................................................................................... 167 5.3. Neural hypotheses ............................................................................................................................... 169 5.3.1. The nigrostriatal dopamine system .................................................................................................. 169 5.3_1.1. Evidence for postsynaptic changes ....................................................................................... 169 5.3.1_2. Evidence forpresynapticchanges ........................................................................................ 172 5.3.1.3_ Dopamine autoreceptor subsensitivity ................................................................................. 176 5.3.1.4. Other hypotheses ............................................................................................................ 179 5.3.2. The mesolimbic and mesocortical dopamine systems ........................................................................... 179 5.3.3. Other neurotransmitter systems ..................................................................................................... 182 5.3.3 1. Opiate peptide-dopamine interactions ................................................................................ 182 5.3.3_2. Norepinephrine .............................................................................................................. 182 5.3.3.3. Serotonin ...................................................................................................................... 183 5.3.3.4. Amino acids ................................................................................................................. 183 5.4. The neural basis of behavioral sensitization: conclusions and a hypothesis .......................................................... 184 6. Generalizability of sensitization ..................................................................................................................... 185 6.1. Stimulants and stress ............................................................................................................................ 185 6.2. Sex differences, stimulants and stress ........................................................................................................ 186 7. Conclusions ............................................................................................................................................. 187 Correspondence." T.E. Robinson, The University of Michigan, Neuroscience Laboratory Building, 1103 E. Huron St., Ann Arbor, MI 48104-1687, U.S.A. 0165-0173/86/$03.50 © 1986 Elsevier Science Publishers B.V. (Biomedical Division)