PT  - JOURNAL ARTICLE
AU  - Luis Orozco-Cabal
AU  - Jie Liu
AU  - Sebastian Pollandt
AU  - Kady Schmidt
AU  - Patricia Shinnick-Gallagher
AU  - Joel P. Gallagher
TI  - Dopamine and Corticotropin-Releasing Factor Synergistically Alter Basolateral Amygdala-to-Medial Prefrontal Cortex Synaptic Transmission: Functional Switch after Chronic Cocaine Administration
AID  - 10.1523/JNEUROSCI.2666-07.2008
DP  - 2008 Jan 09
TA  - The Journal of Neuroscience
PG  - 529--542
VI  - 28
IP  - 2
4099  - http://www.jneurosci.org/content/28/2/529.short
4100  - http://www.jneurosci.org/content/28/2/529.full
SO  - J. Neurosci.2008 Jan 09; 28
AB  - Basolateral amygdala (BLA) neurons provide a major excitatory input to medial prefrontal cortex (mPFC)–layer V pyramidal neurons. Under stressful conditions, commonly associated with chronic cocaine abuse, altered BLA-to-mPFC synaptic transmission could lead to defective emotional information processing and decision making within the mPFC and result in misguided and inappropriate behaviors. We examined the effects of cocaine administered chronically in vivo on EPSCs recorded from a putative BLA–mPFC pathway in vitro and their modulation by dopamine (DA), corticotropin-releasing factor (CRF), and their combination (DA plus CRF). In saline-treated animals, activation of D1/5 receptors depressed BLA–mPFC EPSCs, whereas CRF1 receptor activation alone had no effect on EPSCs. Activating D1/5 and CRF1 receptors in combination, however, worked synergistically through presynaptic and postsynaptic mechanisms to depress EPSCs to levels greater than D1/5 receptor activation alone. After chronic cocaine administration, the function of DA1/5 and CRF receptors switched from inhibitory to excitatory. In slices from cocaine-treated animals, putative BLA–mPFC EPSCs were depressed through a presynaptic mechanism. Now, activation of either D1/5 or CRF2 receptors increased the cocaine-induced, depressed EPSCs. Additionally, simultaneous activation of presynaptic D1/5 and CRF2 receptors led to further enhancement of EPSCs. These data indicate that CRF acting synergistically with DA normally potentiates D1/5-induced synaptic depression. However, after chronic cocaine, the combined synergistic actions of DA and CRF switched polarity to enhance facilitation of BLA–mPFC glutamatergic transmission. Also unmasked after acute withdrawal from chronic cocaine are endogenous, tonic-inhibitory D2-like and tonic-facilitatory CRF2 receptor actions. These multiple functional and receptor changes may underlie the altered, possibly aberrant, decision-making process after chronic cocaine.