Eintrag weiter verarbeiten
Chronic Cocaine Administration Switches Corticotropin-Releasing Factor2Receptor-Mediated Depression to Facilitation of Glutamatergic Transmission in the Lateral Septum
Gespeichert in:
| Zeitschriftentitel: | The Journal of Neuroscience |
|---|---|
| Personen und Körperschaften: | , , , , , , , |
| In: | The Journal of Neuroscience, 25, 2005, 3, S. 577-583 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
Society for Neuroscience
|
| Schlagwörter: |
| Zusammenfassung: | <jats:p>Corticotropin-releasing factor (CRF) and urocortin (Ucn I) are endogenous members among a family of CRF-related peptides that activate two different and synaptically localized G-protein-coupled receptors, CRF<jats:sub>1</jats:sub>and CRF<jats:sub>2</jats:sub>. These peptides and their receptors have been implicated in stress responses and stress with cocaine abuse.</jats:p><jats:p>In this study, we observed significant alterations in excitatory transmission and CRF-related peptide regulation of excitatory transmission in the lateral septum mediolateral nucleus (LSMLN) after chronic cocaine administration. In brain slice recordings from the LSMLN of control (saline-treated) rats, glutamatergic synaptic transmission was facilitated by activation of CRF<jats:sub>1</jats:sub>receptors with CRF but was depressed after activation of CRF<jats:sub>2</jats:sub>receptors with Ucn I. After acute withdrawal from a chronic cocaine administration regimen, CRF<jats:sub>1</jats:sub>activation remained facilitatory, but CRF<jats:sub>2</jats:sub>activation facilitated rather than depressed LSMLN EPSCs. These alterations in CRF<jats:sub>2</jats:sub>effects occurred through both presynaptic and postsynaptic mechanisms. In saline-treated rats, CRF<jats:sub>1</jats:sub>and CRF<jats:sub>2</jats:sub>coupled predominantly to protein kinase A signaling pathways, whereas after cocaine withdrawal, protein kinase C activity was more prominent and likely contributed to the CRF<jats:sub>2</jats:sub>-mediated presynaptic facilitation. Neither CRF nor Ucn I altered monosynaptic GABA<jats:sub>A</jats:sub>-mediated IPSCs before or after chronic cocaine administration, suggesting that loss of GABA<jats:sub>A</jats:sub>-mediated inhibition could not account for the facilitation. This switch in polarity of Ucn I-mediated neuromodulation, from a negative to positive regulation of excitatory glutamatergic transmission after chronic cocaine administration, could generate an imbalance in the brain reward circuitry associated with the LSMLN.</jats:p> |
|---|---|
| Umfang: | 577-583 |
| ISSN: |
0270-6474
1529-2401 |
| DOI: | 10.1523/jneurosci.4196-04.2005 |