Another possibility is that the transient induction of a transcription factor (e.g., ∆FosB, CREB) leads to more permanent changes in gene expression through the modification of chromatin. These and many other transcription factors are believed to activate or repress the transcription of a target gene by promoting the acetylation or deacetylation, respectively, of histones in the vicinity of the gene (42). Although such acetylation and deacetylation of histones can apparently occur very rapidly, it is possible that ∆FosB or CREB might produce longer-lasting adaptations in the enzymatic machinery that controls histone acetylation. ∆FosB or CREB may also promote longer-lived changes in gene expression by regulating other modifications of chromatin (e.g., DNA or histone methylation) that have been implicated in the permanent changes in gene transcription that occur during development (see refs. 42 and 43). Although these possibilities remain speculative, they could provide a mechanism by which transient adaptations to a drug of abuse (or some other perturbation) lead to essentially life-long behavioral consequences.

This work was supported by grants from the National Institute on Drug Abuse.

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Front Matter (R1-R5)

1 Introduction (10994-10995)

2 Neural Roles for Heme Oxygenase: Contrasts to Nitric Oxide Synthase (10996-11002)

3 Presynaptic Kainate Receptors at Hippocampal Mossy Fiber Synapses (11003-11008)

4 Retrograde Signaling at Central Synapses (11009-11015)

5 Controlling Potassium Channel Activities: Interplay Between the Membrane and Intracellular Factors (11016-11023)

6 Calcium Regulation of Neuronal Gene Expression (11024-11031)

7 Sensory Experience and Sensory Activity Regulate Chemosensory Receptor Gene Expression in Caenorhabditis Elegans (11032-11038)

8 Presenilin, Notch, and the Genesis and Treatment of Alzheimer's Disease (11039-11041)

9 FosB: A Sustained Molecular Switch for Addiction (11042-11046)

10 Glutabatergic Modulation of Hyperactivity in Mice Lacking the Dopamine Transporter (11047-11054)

11 Zinc Induces a Src Family Kinase-Medicated Up-Regulation of NMDA Receptor Activity and Excitotoxicity (11055-11061)

12 Regulation of Cyclin-Dependent Kinase 5 and Casein Kinase 1 by Metabotropic Glutamate Receptors (11062-11068)