Research ReportA ventral tegmental CRF–glutamate–dopamine interaction in addiction
Section snippets
Behavioral studies
To explore the possibility that CRF-dependent reinstatement of cocaine-seeking by footshock might involve a CRF action at the level of midbrain dopamine neurons, the Wise group conducted a series of studies in which VTA microdialysis samples were taken and various agents were infused into the VTA by reverse dialysis. First, they prepared animals with chronic jugular catheters and VTA guide cannulae (for subsequent insertion of microdialysis probes) and trained them for two weeks to
Anatomical studies
In parallel with the microdialysis studies of the Wise group, the Morales group initiated anatomical studies on the possible basis for CRF–glutamate–dopamine interaction in the VTA. While the microdialysis studies subsequently showed important differences between cocaine-experienced and cocaine-naive rats, the initial anatomical studies were in cocaine-naive rats and provide an initial characterization of dopamine, glutamate, and CRF elements in the normal VTA.
These studies were designed first
Current status
An interaction of CRF with ventral tegmental glutamate signaling to dopamine neurons, implicated by the electrophysiological studies of Ungless et al. (2003) and first suggested by the histological studies of Swanson et al. (1983) and the intracranial injection studies of Kalivas et al. (1987), is confirmed by our microdialysis and anatomical studies. We have identified CRF–dopamine synapses (Tagliaferro and Morales, 2008) and detected and quantified stress-induced CRF release (Wang et al., 2005
Acknowledgments
Preparation of this manuscript was supported by NIH funding through the Intramural Research Program of the National Institute on Drug Abuse.
References (41)
- et al.
Corticotropin releasing factor (CRF) binding protein: a novel regulator of CRF and related peptides
Front. Neuroendocrinol.
(1995) - et al.
Paradoxical activational effects of a corticotropin-releasing factor-binding protein “ligand inhibitor” in rat brain
Neuroscience
(2000) - et al.
Footshock and conditioned stress increase 3,4dihydroxyphenylacetic acid (DOPAC) in the ventral tegmental area but not substantia nigra
Brain Res.
(1985) - et al.
Drug-induced reinstatement of extinguished self-administration behavior in monkeys
Pharmacol. Biochem. Behav.
(1975) - et al.
Mapping of chemical trigger zones for reward
Neuropharmacology
(2004) - et al.
Self-administration of psychomotor stimulant drugs: the effects of unlimited access
Pharmacol. Biochem. Behav.
(1976) - et al.
On the role of ascending catecholaminergic systems in intravenous self-administration of cocaine
Pharmacol. Biochem. Behav.
(1977) - et al.
Drugs of abuse and stress trigger a common synaptic adaptation in dopamine neurons
Neuron
(2003) - et al.
Corticotropin-releasing factor requires CRF binding protein to potentiate NMDA receptors via CRF receptor 2 in dopamine neurons
Neuron
(2003) - et al.
Displacement of corticotropin releasing factor from its binding protein as a possible treatment for Alzheimer's disease
Nature
(1995)