Background
The advanced stages of addiction are characterized by compulsive drug-seeking and
drug-taking behaviors despite the loss of the hedonic effect of drug consumption.
A pathology of habit forming systems might underlie these features of addiction.
Methods
We have compared use-dependent plasticity of corticostriatal synapses in saline- and
cocaine-treated rats by means of single neuron electrophysiological recordings.
Results
High-frequency stimulation of cortical afferents induced long-term potentiation (LTP)
of corticostriatal synapses in treated and untreated animals. Saline- and acute–cocaine-treated
rats, however, showed synaptic depotentiation in response to subsequent low-frequency
stimulation of the same pathway, whereas chronic cocaine-treated animals were refractory
to this process. Depotentiation was also absent in control slices bathed with cocaine,
dopamine, or with the D1 receptor agonist SKF38393. The effect of cocaine on depotentiation
was prevented by D1 but not D2 dopamine receptor antagonists and was mimicked by pharmacological
inhibition of cyclin-dependent kinase 5, to enhance D1-receptor–associated intracellular
signaling.
Conclusions
These results provide the first evidence that cocaine blocks the reversal of LTP in
brain circuits. This alteration might be important for the persistence of addictive
behavior despite efforts to abstain.
Key Words
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References
- D1 receptor blockade stereospecifically impairs the acquisition of drug-conditioned place preference and place aversion.Behav Pharmacol. 1994; 5: 555-569
- Functional state of corticostriatal synapses determines their expression of short- and long-term plasticity.Synapse. 2000; 38: 271-280
- An investigation of depotentiation of long-term potentiation in the CA1 region of the hippocampus.Exp Brain Res. 1994; 100: 437-443
- Addiction, dopamine, and the molecular mechanisms of memory.Neuron. 2000; 25: 515-532
- Effects of chronic exposure to cocaine are regulated by the neuronal protein Cdk5.Nature. 2001; 410: 376-380
- Phosphorylation of DARPP-32 by Cdk5 modulates dopamine signalling in neurons.Nature. 1999; 402: 669-671
- Levodopa-induced dyskinesia.Ann Neurol. 2000; 47: S60-S68
- Dopamine and cyclic adenosine 3’,5’ monophosphate-regulated phosphoprotein 32 kDa controls both striatal long-term depression and long-term potentiation, opposing forms of synaptic plasticity.J Neurosci. 2000; 20: 8443-8451
- Long-term potentiation in the striatum is unmasked by removing the voltage-dependent blockade of NMDA receptor channel.Eur J Neurosci. 1992; 4: 929-935
- A measure of striatal function predicts motor stereotypy.Nat Neurosci. 2000; 3: 377-383
- Distinct roles of D1 and D5 dopamine receptors in motor activity and striatal synaptic plasticity.J Neurosci. 2003; 23: 8506-8512
- Dopaminergic control of synaptic plasticity in the dorsal striatum.Eur J Neurosci. 2001; 13: 1071-1077
- In vivo activity-dependent plasticity at cortico-striatal connections.Proc Natl Acad Sci U S A. 1997; 94: 7036-7040
- Cyclin-dependent kinase 5 regulates dopaminergic and glutamatergic transmission in the striatum.Proc Natl Acad Sci U S A. 2004; 101: 2191-2196
- Effects of repeated amphetamine treatment on the locomotor activity of the dopamine D1A-deficient mouse.Neuroreport. 1997; 8: 2523-2527
- It could be habit forming.Trends Neurosci. 2003; 26: 184-192
- Levodopa-induced dyskinesias and dopamine-dependent stereotypies.Trends Neurosci. 2000; 23: S71-S77
- Dopamine neurons report an error in the temporal prediction of reward during learning.Nat Neurosci. 1998; 1: 304-309
- Progress in understanding the factors regulating reversibility of long-term potentiation.Rev Neurosci. 2001; 12: 51-68
- Addiction and the brain.Nat Rev Neurosci. 2001; 2: 695-703
- Building neural representations of habit.Science. 1999; 286: 1745-1749
- Dopamine D1/D5 receptor activation is required for long-term potentiation in the rat neostriatum in vitro.J Neurophysiol. 2001; 85: 117-124
- Compulsive use of dopamine replacement therapy in Parkinson’s disease.Lancet Neurol. 2003; 2: 595-604
- Cyclin-dependent kinase 5 phosphorylates the N-terminal domain of the postsynaptic density protein PSD-95 in neurons.J Neurosci. 2004; 24: 865-876
- Involvement of a calcineurin/inhibitor-1 phosphatase cascade in hippocampal long-term depression.Nature. 1994; 369: 486-488
- From neurobiology to treatment.Nat Neurosci. 2002; 5: 1076-1079
- Molecular mechanisms of drug addiction.Mol Psychiatry. 1996; 1: 190-199
- Amplification of dopaminergic signaling by a positive feedback loop.Proc Natl Acad Sci U S A. 2000; 97: 12840-12845
- Expression of long-term potentiation of the striatum in methamphetamine-sensitized rats.Neurosci Lett. 1999; 268: 81-84
- Low-frequency stimulation erases LTP through an NMDA receptor-mediated activation of protein phosphatases.Learn Mem. 1994; 1: 129-139
- D1/D5 dopamine receptors inhibit depotentiation at CA1 synapses via cAMP-dependent mechanism.J Neurosci. 1998; 18: 1270-1279
- Learning and memory functions of the basal ganglia.Annu Rev Neurosci. 2002; 25: 563-593
- Regional and postnatal heterogeneity of activity-dependent long-term changes in synaptic efficacy in the dorsal striatum.J Neurophysiol. 2000; 84: 1422-1429
- Loss of bidirectional striatal synaptic plasticity in L-DOPA-induced dyskinesia.Nat Neurosci. 2003; 6: 501-506
- Abnormal Ca2+-calmodulin-dependent protein kinase II function mediates synaptic and motor deficits in experimental parkinsonism.J Neurosci. 2004; 24: 5283-5291
- A cellular mechanism of reward-related learning.Nature. 2001; 413: 67-70
- Substantia nigra dopamine regulates synaptic plasticity and membrane potential fluctuations in the rat neostriatum, in vivo.Neuroscience. 2000; 99: 199-203
- Drug addiction.Nature. 1999; 398: 567-570
- Predictive reward signal of dopamine neurons.J Neurophysiol. 1998; 80: 1-27
- Getting formal with dopamine and reward.Neuron. 2002; 36: 241-263
- Postsynaptic signaling and plasticity mechanisms.Science. 2002; 298: 776-780
- Extinction-induced upregulation in AMPA receptors reduces cocaine-seeking behaviour.Nature. 2003; 421: 70-75
- Diverse psychotomimetics act through a common signaling pathway.Science. 2003; 302 (1412–145)
- Increased activity of cyclin-dependent kinase 5 leads to attenuation of cocaine-mediated dopamine signaling.Proc Natl Acad Sci USA. 2005; 102: 1737-1742
- Long-term depression in the nucleus accumbens.Nat Neurosci. 2001; 4: 1217-1223
- Measuring reward with the conditioned place preference paradigm.Prog Neurobiol. 1998; 56: 613-672
- Single cocaine exposure in vivo induces long-term potentiation in dopamine neurons.Nature. 2001; 411: 583-587
- Effect of nigrostriatal dopamine depletion on the post-training, memory improving action of amphetamine.Life Sci. 1988; 43: 7-12
Article info
Publication history
Published online: February 14, 2006
Accepted:
November 28,
2005
Received in revised form:
November 10,
2005
Received:
April 4,
2005
Identification
Copyright
© 2006 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
