Persistent Structural Modifications in Nucleus Accumbens and Prefrontal Cortex Neurons Produced by Previous Experience with Amphetamine

Experience-dependent changes in behavior are thought to involve structural modifications in the nervous system, especially alterations in patterns of synaptic connectivity. Repeated experience with drugs of abuse can result in very long-lasting changes in behavior, including a persistent hypersensitivity (sensitization) to their psychomotor activating and rewarding effects. It was hypothesized, therefore, that repeated treatment with the psychomotor stimulant drug amphetamine, which produces robust sensitization, would produce structural adaptations in brain regions that mediate its psychomotor activating and rewarding effects. Consistent with this hypothesis, it was found that amphetamine treatment altered the morphology of neurons in the nucleus accumbens and prefrontal cortex. Exposure to amphetamine produced a long-lasting (>1 month) increase in the length of dendrites, in the density of dendritic spines, and in the number of branched spines on the major output cells of the nucleus accumbens, the medium spiny neurons, as indicated by analysis of Golgi-stained material. Amphetamine treatment produced similar effects on the apical (but not basilar) dendrites of layer III pyramidal neurons in the prefrontal cortex. The ability of amphetamine to alter patterns of synaptic connectivity in these structures may contribute to some of the long-term behavioral consequences of repeated amphetamine use, including amphetamine psychosis and addiction.

[1]  R. Karler,et al.  Blockade of behavioral sensitization to cocaine and amphetamine by inhibitors of protein synthesis , 1993, Brain Research.

[2]  T. Robinson,et al.  Amphetamine‐Induced time‐dependent sensitization of dopamine neurotransmission in the dorsal and ventral striatum: A microdialysis study in behaving rats , 1995, Synapse.

[3]  F. Morrell,et al.  Perforated synapses on double-headed dendritic spines: a possible structural substrate of synaptic plasticity , 1989, Brain Research.

[4]  P. Groves,et al.  Three-dimensional structure of dendritic spines in the rat neostriatum , 1983, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[5]  T. Robinson,et al.  Enduring changes in brain and behavior produced by chronic amphetamine administration: A review and evaluation of animal models of amphetamine psychosis , 1986, Brain Research Reviews.

[6]  G. Paxinos,et al.  The Rat Brain in Stereotaxic Coordinates , 1983 .

[7]  A. D. Smith,et al.  Convergence of hippocampal and dopaminergic input onto identified neurons in the nucleus accumbens of the rat. , 1989, Journal of chemical neuroanatomy.

[8]  P. Goldman-Rakic,et al.  Dopamine synaptic complex with pyramidal neurons in primate cerebral cortex. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[9]  A. Carlsson,et al.  Interactions between glutamatergic and monoaminergic systems within the basal ganglia-implications for schizophrenia and Parkinson's disease , 1990, Trends in Neurosciences.

[10]  John F. Marshall,et al.  The mesolimbic dopamine system: From motivation to action , 1991 .

[11]  S. Schenk,et al.  Persistence of the ability of amphetamine preexposure to facilitate acquisition of cocaine self-administration , 1994, Pharmacology Biochemistry and Behavior.

[12]  B. Kolb,et al.  Age, Experience and the Changing Brain , 1998, Neuroscience & Biobehavioral Reviews.

[13]  P. Goldman-Rakic,et al.  The anatomy of dopamine in monkey and human prefrontal cortex. , 1992, Journal of neural transmission. Supplementum.

[14]  E. Gray,et al.  Axo-somatic and axo-dendritic synapses of the cerebral cortex: an electron microscope study. , 1959, Journal of anatomy.

[15]  F. J. White,et al.  Repeated administration of cocaine or amphetamine alters neuronal responses to glutamate in the mesoaccumbens dopamine system. , 1995, The Journal of pharmacology and experimental therapeutics.

[16]  F. Bloom,et al.  Cellular and molecular mechanisms of drug dependence. , 1988, Science.

[17]  S. Sesack,et al.  Prefrontal cortical efferents in the rat synapse on unlabeled neuronal targets of catecholamine terminals in the nucleus accumbens septi and on dopamine neurons in the ventral tegmental area , 1992, The Journal of comparative neurology.

[18]  R. Guillery,et al.  Dopamine nerve terminal degeneration produced by high doses of methylamphetamine in the rat brain , 1982, Brain Research.

[19]  W. Greenough,et al.  Plasticity of Synapse Structure and Pattern in the Cerebral Cortex , 1988 .

[20]  K. Berridge,et al.  The neural basis of drug craving: An incentive-sensitization theory of addiction , 1993, Brain Research Reviews.

[21]  Dale Purves,et al.  Neural Activity And The Growth Of The Brain , 1994 .

[22]  J. Rushen.  Neural activity and the growth of the brain , 1995 .

[23]  T. Robinson,et al.  Regional Differences in the Effects of Amphetamine Withdrawal on Dopamine Dynamics in the Striatum , 1996, Neuropsychopharmacology.

[24]  D. Sholl.  The organization of the cerebral cortex , 1957 .

[25]  R. Wise,et al.  Rewarding Actions of Phencyclidine and Related Drugs in Nucleus Accumbens Shell and Frontal Cortex , 1996, The Journal of Neuroscience.

[26]  W. Greenough,et al.  Increased Density of Multiple-Head Dendritic Spines on Medium-Sized Spiny Neurons of the Striatum in Rats Reared in a Complex Environment , 1996, Neurobiology of Learning and Memory.

[27]  B. Kolb,et al.  Cryostat sectioning of Golgi-Cox tissue. , 1986, Stain technology.

[28]  T. Robinson,et al.  Long-lasting effects of escalating doses of d-amphetamine on brain monoamines, amphetamine-induced stereotyped behavior and spontaneous nocturnal locomotion , 1987, Pharmacology Biochemistry and Behavior.

[29]  W. Greenough.  Structural correlates of information storage in the mammalian brain: a review and hypothesis , 1984, Trends in Neurosciences.

[30]  B. Kolb,et al.  Nerve growth factor stimulates growth of cortical pyramidal neurons in young adult rats , 1997, Brain Research.

[31]  P. Kalivas,et al.  Dopamine transmission in the initiation and expression of drug- and stress-induced sensitization of motor activity , 1991, Brain Research Reviews.

[32]  A. Peters,et al.  The projection of the lateral geniculate nucleus to area 17 of the rat cerebral cortex. I. General description , 1976, Journal of neurocytology.

[33]  A. D. Smith,et al.  The neural network of the basal ganglia as revealed by the study of synaptic connections of identified neurones , 1990, Trends in Neurosciences.

[34]  K. Harris,et al.  Dendritic spines of rat cerebellar Purkinje cells: serial electron microscopy with reference to their biophysical characteristics , 1988, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[35]  S. B. Kater,et al.  Dendritic spines: cellular specializations imparting both stability and flexibility to synaptic function. , 1994, Annual review of neuroscience.

[36]  C. H. Bailey,et al.  The anatomy of a memory: convergence of results across a diversity of tests , 1988, Trends in Neurosciences.

[37]  Gray Eg.  Axo-somatic and axo-dendritic synapses of the cerebral cortex: An electron microscope study , 1959 .

[38]  F. J. White,et al.  Repeated cocaine administration causes persistent enhancement of D1 dopamine receptor sensitivity within the rat nucleus accumbens. , 1991, The Journal of pharmacology and experimental therapeutics.

[39]  K. Berridge,et al.  The Mind of an Addicted Brain: Neural Sensitization of Wanting Versus Liking , 1995 .

[40]  P. Groves,et al.  Histological and ultrastructural evidence thatd-amphetamine causes degeneration in neostriatum and frontal cortex of rats , 1990, Brain Research.

[41]  R. Wise,et al.  A psychomotor stimulant theory of addiction. , 1987, Psychological review.

[42]  A. Peters.  Projection of Lateral Geniculate Nucleus to Area 17 of the Rat Cerebral Cortex , 1976 .

[43]  Prof. Dr. Karl Zilles.  The Cortex of the Rat , 1985, Springer Berlin Heidelberg.

[44]  K M Harris,et al.  Three‐dimensional analysis of the structure and composition of CA3 branched dendritic spines and their synaptic relationships with mossy fiber boutons in the rat hippocampus , 1992, The Journal of comparative neurology.

[45]  S. Sesack,et al.  In the rat medial nucleus accumbens, hippocampal and catecholaminergic terminals converge on spiny neurons and are in apposition to each other , 1990, Brain Research.

[46]  B. Berger,et al.  Dopaminergic innervation of the cerebral cortex: unexpected differences between rodents and primates , 1991, Trends in Neurosciences.