Acute and Chronic Corticotropin-Releasing Factor 1 Receptor Blockade Inhibits Cocaine-Induced Dopamine Release: Correlation with Dopamine Neuron Activity

Abstract

Corticotropin-releasing factor (CRF) is a neuropeptide associated with the integration of the physiological and behavioral responses to stress. Recently, CRF 1 receptor antagonists have been shown to decrease cocaine self-administration and inhibit stress-induced reinstatement of cocaine-seeking behavior. The exact mechanisms underlying this effect are not clear. Based on the large amount of literature demonstrating an association between dopaminergic neurotransmission and reward-related behavior, the aim of the present study was to examine the effects of acute versus chronic CRF 1 receptor blockade on mesencephalic dopamine (DA) neuron activity (determined by in vivo extracellular recordings) and extracellular DA levels in the nucleus accumbens (Acb) (using in vivo microdialysis). In addition, the effect of CRF 1 receptor antagonism on cocaineinduced DA overflow in the Acb was examined and correlated with DA neuron activity in the ventral tegmental area (VTA).Acute (but not chronic) CRF 1 receptor blockade by CRA-0450 [1-[8-(2,4-dichlorophenyl)-2-methylquinolin-4-yl]-1,2,3,6-tetrahydropyridine-4-carboxamide benzenesulfonate] was found to significantly increase DA neuron population activity without affecting burst firing, average firing rate, or Acb DA levels. In addition, both acute and chronic CRF 1 receptor antagonism significantly reduced cocaine-stimulated DA overflow in the Acb, and this reduction was correlated with an attenuated cocaine-induced inhibition of DA population activity. Taken as a whole, these data demonstrate that, although DA neuron population activity exhibits tolerance to chronic CRF 1 receptor antagonism (by CRA-0450), tolerance does not develop to the selective inhibition of cocaine-induced DA release (in the Acb) and, as such, may be beneficial in the treatment of cocaine addiction.

Withdrawal from Acute Amphetamine Induces an Amygdala-Driven Attenuation of Dopamine Neuron Activity: Reversal by Ketamine

“…Because of activation of DA autoreceptors and long-loop feedback pathways from forebrain structures, these drugs also inhibit DA cell firing (Einhorn et al, 1988;Lodge and Grace, 2005) via activation of D1 and D2 receptors (Shi et al, 2000). In the present study, we show a decrease in the percentage of spikes in bursts of DA neurons after acute amphetamine (A+1), consistent with previous work (Lodge and Grace, 2005).…”

Perturbations in Effort-Related Decision-Making Driven by Acute Stress and Corticotropin-Releasing Factor

“…Conversely, a recent report by Twining et al (2015) showed that reductions in nucleus accumbens dopamine transmission induced by an aversive tastant was reversed by administration of a CRF antagonist into the VTA. Similarly, ICV administration of a CRF 1 antagonist increases dopamine neuron population activity and mesoaccumbens dopamine release, 'suggestive of a tonic inhibitory role for CRF on the activity of VTA dopamine neurons' (Lodge and Grace, 2005). Collectively, these previous findings suggest that CRF in the VTA can at least in some instances act in a stimulus-specific manner to attenuate dopamine release, putatively by reducing glutamate and/or enhancing GABA release onto dopamine neurons in the VTA.…”

Stressor- and corticotropin releasing factor-induced reinstatement and active stress-related behavioral responses are augmented following long-access cocaine self-administration by rats

“…Although we hypothesize that augmented CRF-induced reinstatement was due to alterations in CRF-R2 activity, it is also possible that alterations in CRF-R1 receptors contributed to the effect. CRF-R1 antagonists have been reported to reduce cocaine SA (Goeders and Guerin 2000), cocaineinduced increases in NAcc DA (Lodge and Grace 2005), cocaine-induced conditioned place preference (Lu et al 2003) and stressor-but not cocaine-induced reinstatement Lee et al 2003).…”