HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Full Text (PDF) All Versions of this Article: 97/1/937    most recent 00349.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (6) Citing Articles via Google Scholar Google Scholar Articles by Fu, Y. Articles by Shinnick-Gallagher, P. Search for Related Content PubMed PubMed Citation Articles by Fu, Y. Articles by Shinnick-Gallagher, P.

REPORT

Long-Term Potentiation (LTP) in the Central Amygdala (CeA) Is Enhanced After Prolonged Withdrawal From Chronic Cocaine and Requires CRF₁ Receptors

Department of Pharmacology and Toxicology, University of Texas, Medical Branch, Galveston, Texas

Submitted 5 April 2006; accepted in final form 26 October 2006

	ABSTRACT

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION GRANTS ACKNOWLEDGMENTS REFERENCES

 
The amygdala is part of the brain reward circuitry that plays a role in cocaine-seeking and abstinence in animals and cocaine craving and relapse in humans. Cocaine-seeking is elicited by cocaine-associated cues, and the basolateral amygdala (BLA) and CeA are essential in forming and communicating drug-related associations that are thought to be critical in long-lasting relapse risk associated with drug addiction. Here we simulated a cue stimulus with high-frequency stimulation (HFS) of the BLA–CeA pathway to examine mechanisms that may contribute to drug-related associations. We found enhanced long-term potentiation (LTP) after 14-day but not 1-day withdrawal from 7-day cocaine treatment mediated through N-methyl-D-aspartate (NMDA) receptors (NRs), L-type voltage-gated calcium channels (L-VGCCs), and corticotropin-releasing factor (CRF)₁ receptors; this was accompanied by increased phosphorylated NR1 and CRF₁ protein not associated with changes in NMDA/AMPA ratios in amygdalae from cocaine-treated animals. We suggest that these signaling mechanisms may provide therapeutic targets for the treatment of cocaine cravings.

	INTRODUCTION

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION GRANTS ACKNOWLEDGMENTS REFERENCES

 
The amygdala is essential in forming stimulus–reward associations and associational processing of conditioned cues (Aggleton 1992; Shinnick-Gallagher et al. 2003). Drug-associated cues can induce craving in cocaine users and alter neural activity in the amygdala (Childress et al. 1999), and electrical stimulation of the basolateral amygdala (BLA) can reinstate drug-seeking in animals (Hayes et al. 2003). Drug-cue associations are not well understood, but the mechanisms may be similar to forms of synaptic plasticity and the induction and expression of cocaine sensitization, a model for long-term neuroadaptations important in addiction (De Vries et al. 1999; Kalivas and Alesdatter 1993; Robinson and Berridge 1993). Antagonizing N-methyl-D-aspartate (NMDA) receptors (NRs) in the amygdala can prevent and block locomotor sensitizing effects of chronic cocaine (Kalivas and Alesdatter 1993), and amygdala NR1 protein levels are increased after acute and chronic cocaine (Turchan et al. 2003). Likewise, activation of L-type calcium channels mimics the induction (Lin et al. 2001) and antagonists block expression of cocaine sensitization (Pierce et al. 1998). Furthermore, corticotropin-releasing factor (CRF) systems in the amygdala play a significant role in cocaine addiction (Sarnyai et al. 2001). In cocaine-treated animals, CRF release in the amygdala is enhanced during acute withdrawal (Richter and Weiss 1999) and in response to a cocaine challenge (Richter et al. 1995). Amygdala CRF immunolabeling decreases after short-term, but increases after long-term withdrawal from chronic cocaine (Zorrilla et al. 2001). Furthermore, cocaine-induced locomotor activity is blocked by intracerebroventricular injection of a CRF antagonist (Sarnyai et al. 1992). These data provide strong rationale for testing the role of CRF receptors in synaptic plasticity in the central amygdala (CeA). This study shows that specific cocaine treatment and withdrawal paradigms resulted in enhanced synaptic plasticity, that NR, L-type calcium channels, and CRF₁ were required for long-term potentiation (LTP) in the BLA–CeA pathway, and that phosphorylated-NR1 (P-NR1) and CRF₁ protein but not synaptic potentials were increased after withdrawal from chronic cocaine.

	METHODS

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION GRANTS ACKNOWLEDGMENTS REFERENCES

 
Cocaine HCl was a gift from the National Institute of Drug Abuse. Male Sprague-Dawley albino rats (Harlan, 4–6 wk) were injected daily with cocaine (15 mg/kg, ip) or saline (0.1 ml/kg, ip), once or twice per day for 1 or 2 wk to assess how duration and frequency of cocaine treatment and withdrawal time influence synaptic plasticity. Behavioral sensitization measuring the progressive locomotor stimulant properties resulting from chronic cocaine treatment was analyzed with a photocell apparatus before and on the first and last days of cocaine or saline treatment (Fig. 1E) as a measure of cocaine's effectiveness. After 7 days, locomotor activity was increased significantly over 1-day activity in the cocaine-treated (F_1,120 = 260.07, P < 0.001) but not in the saline-treated (P > 0.05) group. No significant differences were observed between animals injected once per day for 7 days or twice daily for 14 days. Coronal brain slices (500 µm) were prepared and incubated at room temperature for 1 h with oxygenated, modified artificial cerebrospinal fluid (ACSF) solution (in mM): 119 NaCl, 3.0 KCl, 1.2 NaH₂PO₄, 1.2 MgSO₄, 2.5 CaCl₂, 25 NaHCO₃, and 11.5 glucose. They were then submerged in a chamber (1.0 ml, 2.5 ml/min) at 30 ± 1°C for another hour before recording. BLA fibers were stimulated with concentric electrodes (50 k) using 150-µs pulses of varying intensity (3–15 V) at 0.05 Hz, and field excitatory postsynaptic potentials (fEPSPs) were recorded in the capsula/medial CeA with tungsten electrodes (2–5 M). fEPSP magnitude was adjusted to 30% of maximum response and baseline recorded, and LTP was induced using high-frequency stimulation (HFS) consisting of five trains of stimuli (100 Hz for 1 s, 3-min intervals). fEPSPs were recorded at 0.05 Hz for another hour, and their slopes were normalized to baseline values. A one- or two-tailed unpaired t-test or one-way ANOVA with appropriate post hoc tests were used for statistical analysis; n equals the number of slices. Methodologies for patch recording (Liu et al. 2004) and Western blot analysis (Zinebi et al. 2003) were similar to that reported previously.

View larger version (33K): [in this window] [in a new window]   FIG. 1. Long-term potentiation (LTP) at the basolateral amygdala (BLA)–central amygdala (CeA) pathway was enhanced after 2-wk (B) but not 24-h (A) withdrawal from chronic cocaine without changes in single field excitatory postsynaptic potential (fEPSP) responsiveness (D). A and B: traces above indicated fEPSPs before and after high-frequency stimulation (HFS)-LTP at the times indicated in the bottom graphs, showing summary data of LTP time-course. C: plot of last 10 fEPSPs (mean ± SE) 1 h after LTP induction showed enhanced LTP after 7- and 14-day cocaine tratment and 14-day withdawal but not after 14-day treatment and 24-h withdrawal. Time-course of 7-day treatment and 14-day withdrawal is shown in Figs. 2 and 3. D: input–output relationships are not altered in any treatment paradigm. E: horizontal locomotor activity is enhanced after 7 days of cocaine treatment, suggesting behavior sensitization. Calibrations are the same in A and B.

	RESULTS

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION GRANTS ACKNOWLEDGMENTS REFERENCES

Previously, we showed that HFS-LTP in the BLA–CeA pathway depends on NRs and L-VGCCs (Fu and Shinnick-Gallagher 2005). To examine whether induction mechanisms were altered in cocaine-enhanced LTP (Fig. 2), slices were superfused with the NMDA antagonist APV (50 µM) in ACSF or the L-VGCC antagonist nimodipine (NIM, 10 µM) 15 min before HFS. APV blocked LTP both in cocaine (control: 202.1 ± 12.1%, n = 12; APV: 110.4 ± 2.4%, n = 5, P < 0.001) and saline (control: 160.1 ± 9.0%, n = 12; APV: 107.7 ± 7.4%, n = 5, P < 0.005) groups. Similarly, NIM blocked LTP in cocaine-treated (control: 202.1 ± 12.1%, n = 12; NIM: 104.0 ± 11.8%, n = 5, P < 0.001) and saline-treated (control: 160.1 ± 9.0%, n = 12; NIM: 109.0 ± 7.7%, n = 5, P < 0.005) groups. These data indicated that NMDA receptors and L-VGCCs are necessary for LTP induction by HFS in cocaine and saline treatment groups.

View larger version (39K): [in this window] [in a new window]   FIG. 2. LTP in the BLA pathway is dependent on N-methyl-D-aspartate (NMDA) receptors (A and B) and L-type voltage-gated calcium channels (L-VGCCs) (C and D) in slices 14 days after 7-day treatment with either saline (left) or cocaine (right). In each panel, numbered traces show responses before and after HFS at times indicated in graph in slices from saline (A and C)- and cocaine (B and D)-treated animals in presence and absence of APV (A and B) or nimodipine (NIM; C and D). Graphs below show summary date of LTP time-course in slices from saline (A and C)- and cocaine (B and D)-treated groups in the presence and absence of APV (A and B) or NIM (C and D). The same control data are plotted for saline (A, C, and Fig. 3C) and cocaine (B, D, and Fig. 3D). Calibrations in B–D are the same as in A.

View larger version (32K): [in this window] [in a new window]   FIG. 3. LTP in BLA–CeA pathway is dependent on corticotropin-releasing factor (CRF)1 receptors in saline- and cocaine-treated populations and P-NR1, and CRF1 protein is increased in cocaine-treated populations. A and B: numbered top traces recorded in slices from saline (A)- and cocaine (B)-treated groups show fEPSPs before and after HFS-induced LTP at times indicated in the bottom graphs, which show summary data for LTP time-course. C: Western blots for NR1 (Santa Cruz), P-NR1 (Upstate), and CRF1 (Santa Cruz) protein (top blots) and corresponding actin (Santa Cruz) protein (bottom blots) are expressed as optical density ratios in the summary graphs below. The same control data are plotted for saline (C and Fig. 2, A and C) and cocaine (D and Fig. 2, B and D).

	DISCUSSION

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION GRANTS ACKNOWLEDGMENTS REFERENCES

 
Our studies show for the first time that LTP in the BLA–CeA pathway was enhanced after long- but not short-term withdrawal from chronic cocaine, that HFS-induced LTP was modulated endogenously by CRF₁, and that elevated P-NR1 and CRF₁ protein may contribute to cocaine-enhanced LTP. The withdrawal-induced enhancement of LTP may be related to the neuroadaptive effects associated with behavioral sensitization that can persist for 2 wk (Kalivas et al. 1988) and that may have a component of associative contextual conditioning (Carey and Gui 1998). Markers for BLA neuronal activity increase in animals exposed to a cocaine environment (Brown et al. 1992; Neisewander et al. 2000; Thomas et al. 2003) even after 4-mo withdrawal (Ciccocioppo et al. 2001). Thus stimulating the BLA may simulate neuronal activity during cue exposure after the animal has been sensitized.

Cocaine-enhanced LTP in the BLA–CeA pathway was critically dependent on withdrawal, whereas baseline fEPSP responsiveness was unchanged. After 4- to 6-day withdrawal after 5-day cocaine treatment, hippocampal LTP was enhanced (Thompson et al. 2002), but after 100-day withdrawal and at higher self-administered cocaine doses, LTP was reduced (Thompson et al. 2004); these effects were also not correlated with an altered fEPSP amplitude. Conversely, at an intralateral amygdala (LA) synapse, an increased baseline response and reduced LTP were observed with cocaine treatment (15 mg/kg, 3 times per day, 1-h intervals for 7 days) and 1- to 3-day withdrawal, but the effect dissipated within 9 days; this reduction in LTP was interpreted as occlusion caused by the facilitated baseline EPSP response (Goussakov et al. 2006). Functionally, these data indicated that long-lasting effects of cocaine were consistently revealed with HFS. Although disparities in findings suggest that changes in synaptic facilitation and plasticity are dependent on brain area, synapse, and treatment paradigm, the studies provide insight into the relative persistence of the effects of cocaine treatment.

HFS-LTP at the BLA–CeA synapse is dependent on NMDA receptors and L-VGCCs. After 2-wk withdrawal from chronic cocaine, NR2B and NR1 subunits are upregulated in other brain areas (Loftis and Janowsky 2000). Here we report a similar increase in P-NR1 protein in the amygdala, which could contribute to the enhanced HFS-LTP after chronic cocaine. However, changes in NMDA/AMPA ratios were not detected, suggesting that the increased P-NR1 proteins may not be accessible to transmitter evoked with single stimuli at this synapse. Cocaine withdrawal also increases calcium entry through L-VGCCs (Nasif et al. 2005), and L-VGCC antagonists block establishment of conditioned locomotion by cocaine (Reimer and Martin-Iverson 1994), suggesting that greater L-VGCC activity in cocaine withdrawn animals could contribute to the cocaine-enhanced HFS-LTP. However, it is unlikely that increased L-VGCC activity contributed to the cocaine-enhanced LTP because 1C subunit protein was unchanged in the cocaine group. CRF₂ receptor activation potentiated NMDA responses in ventral tegmental area neurons (Ungless et al. 2003) but CRF₂ was not involved in HFS-LTP in the BLA–CeA pathway, and amygdala CRF₂ protein was not increased with chronic cocaine. These data suggest that L-type VGCCs or CRF₂ receptors may not play a role in the cocaine-enhanced LTP, whereas increased P-NR1 protein may contribute to enhanced HFS-LTP but not to singly evoked EPSPs at the BLA–CeA synapse.

Although the CRF₁ antagonist did not affect baseline fEPSPs, subsequent HFS failed to induce LTP in slices from cocaine and saline groups, indicating that CRF₁ receptors are required for LTP induction. We previously showed that exogenous CRF directly enhanced mEPSC frequency in the CeA, suggesting a presynaptic increase in glutamate release (Liu et al. 2004). Repetitively stimulating cerebellar afferents is known to release CRF (Tian and Bishop 2003), and afferent stimulation (foot-shock) can increase endogenous CRF release in the CeA and BLA (Roozendaal et al. 2002). These results suggested that HFS could enhance endogenous CRF release in the CeA. CRF priming enhances HFS-induced LTP (Blank et al. 2002), CRF itself can induce LTP in the hippocampus (Wang et al. 1998), and at LA–CeA (Pollandt et al. 2006) and BLA–CeA (Fu et al. 2004) synapses, and CRF-induced LTP is enhanced after chronic cocaine. Furthermore, both CRF₁ protein (Radulovic et al. 1998) and mRNA (Chalmers et al. 1995) are found in the BLA, and CRF₁ receptors are located on excitatory type terminals in the CeA (Chalmers et al. 1995), suggesting an anatomical basis for a CRF₁-mediated effect on glutamate release. The block of HFS-LTP by the CRF₁ antagonist, increase in CRF₁ protein, and enhanced responsiveness to CRF in the BLA–CeA pathway (Fu et al. 2004) after cocaine withdrawal suggests that endogenously released CRF acting through CRF₁ receptors contributes to the enhanced LTP in cocaine. CRF is known to enhance locally evoked GABA inhibition in the CeA through CRF₁ receptors (Nie et al. 2004). With GABA inhibition intact, we previously found that low CRF concentrations inhibited evoked excitatory postsynaptic currents (EPSCs) 40%, whereas in the presence of GABA antagonists, CRF inhibited miniature EPSCs by only 20% (Liu et al. 2004), indicating that one half of CRF-induced inhibition of evoked EPSCs may be caused by CRF-induced GABA release. However, HFS-LTP in this pathway is not significantly altered by GABA antagonists (Fu and Shinnick-Gallagher 2005), and GABA antagonists did not affect NBI inhibition of HFS-LTP (data not shown). Altogether the results suggest that an HFS-induced increase in CRF release in the presence of GABA antagonists resulted in facilitated glutamate release, which prevailed over an inhibitory effect and induced LTP.

Furthermore, our data suggest that increases in P-NR1 and CRF₁ protein and/or their downstream signaling mechanisms may contribute to the cocaine-enhanced LTP at the BLA–CeA synapse.

	GRANTS

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION GRANTS ACKNOWLEDGMENTS REFERENCES

 
This work was supported by National Institute of Drug Abuse Grants DA-017727 to P. Shinnick-Gallagher and DA-011991 to J. P. Gallagher.

	ACKNOWLEDGMENTS

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION GRANTS ACKNOWLEDGMENTS REFERENCES

 
The authors thank K. Schmidt for helpful comments on the manuscript.

	FOOTNOTES

 
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Address for reprint requests and other correspondence: P. Shinnick-Gallagher, 301 University Blvd., Galveston, TX 77555-1031 (E-mail: psgallag{at}utmb.edu)

	REFERENCES

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION GRANTS ACKNOWLEDGMENTS REFERENCES

 
Aggleton JP. The Amygdala: Neurobiological Aspects of Emotion, Memory, and Mental Dysfunction. New York: WileyLiss, 1992.

Blank T, Nijholt I, Eckart K, Spiess J. Priming of long-term potentiation in mouse hippocampus by corticotropin-releasing factor and acute stress: implications for hippocampus-dependent learning. J Neurosci 22: 3788–3794, 2002.[Abstract/Free Full Text]

Brown EE, Robertson GS, Fibiger HC. Evidence for conditional neuronal activation following exposure to a cocaine-paired environment: role of forebrain limbic structures. J Neurosci 12: 4112–4121, 1992.[Abstract]

Carey RJ, Gui J. Cocaine conditioning and cocaine sensitization: what is the relationship. Behav Brain Res 92: 67–76, 1998.[CrossRef][Web of Science][Medline]

Chalmers DT, Lovenberg TW, De Souza EB. Localization of novel corticotropin-releasing factor receptor (CRF2) mRNA expression to specific subcortical nuclei in rat brain: comparison with CRF1 receptor mRNA expression. J Neurosci 15: 6340–6350, 1995.[Abstract/Free Full Text]

Childress AR, Mozley PD, McElgin W, Fitzgerald J, Reivich M, O'Brien CP. Limbic activation during cue-induced cocaine craving. Am J Psychiatry 156: 11–18, 1999.[Abstract/Free Full Text]

Ciccocioppo R, Sanna PP, Weiss F. Cocaine-predictive stimulus induces drug-seeking behavior and neural activation in limbic brain regions after multiple months of abstinence: reversal by D(1) antagonists. Proc Natl Acad Sci USA 98: 1976–1981, 2001.[Abstract/Free Full Text]

De Vries TJ, Schoffelmeer AN, Binnekade R, Vanderschuren LJ. Dopaminergic mechanisms mediating the incentive to seek cocaine and heroin following long-term withdrawal of IV drug self-administration. Psychopharmacology (Berl) 143: 254–260, 1999.[CrossRef][Medline]

Fu Y, Liu J, Gallagher JP, Shinnick-Gallagher P. Cocaine withdrawal enhances corticotropin releasing factor (CRF) dependent long-term potentiation (LTP) in the central amygdala. Soc Neurosci Abstr 855: 14, 2004.

Fu Y, Shinnick-Gallagher P. Two intra-amygdaloid pathways to the central amygdala exhibit different mechanisms of long-term potentiation. J Neurophysiol 93: 3012–3015, 2005.[Abstract/Free Full Text]

Goussakov I, Chartoff EH, Tsvetkov E, Gerety LP, Meloni EG, Carlezon WA, Bolshakov VY. LTP in the lateral amygdala during cocaine withdrawal. Eur J Neurosci 23: 239–250, 2006.[CrossRef][Web of Science][Medline]

Hayes RJ, Vorel SR, Spector J, Liu X, Gardner EL. Electrical and chemical stimulation of the basolateral complex of the amygdala reinstates cocaine-seeking behavior in the rat. Psychopharmacology (Berl) 168: 75–83, 2003.[CrossRef][Medline]

Kalivas PW, Alesdatter JE. Involvement of N-methyl-D-aspartate receptor stimulation in the ventral tegmental area and amygdala in behavioral sensitization to cocaine. J Pharmacol Exp Ther 267: 486–495, 1993.[Abstract/Free Full Text]

Kalivas PW, Duffy P, DuMars LA, Skinner C. Behavioral and neurochemical effects of acute and daily cocaine administration in rats. J Pharmacol Exp Ther 245: 485–492, 1988.[Abstract/Free Full Text]

Lin CH, Yeh SH, Lin CH, Lu KT, Leu TH, Chang WC, Gean PW. A role for the PI-3 kinase signaling pathway in fear conditioning and synaptic plasticity in the amygdala. Neuron 31: 841–851, 2001.[CrossRef][Web of Science][Medline]

Liu J, Yu B, Neugebauer V, Grigoriadis DE, Rivier J, Vale WW, Shinnick-Gallagher P, Gallagher JP. Corticotropin-releasing factor and Urocortin I modulate excitatory glutamatergic synaptic transmission. J Neurosci 24: 4020–4029, 2004.[Abstract/Free Full Text]

Liu J, Yu B, Orozco-Cabal L, Grigoriadis DE, Rivier J, Vale WW, Shinnick-Gallagher P, Gallagher JP. Chronic cocaine administration switches corticotropin-releasing factor2 receptor-mediated depression to facilitation of glutamatergic transmission in the lateral septum. J Neurosci 25: 577–583, 2005.[Abstract/Free Full Text]

Loftis JM, Janowsky A. Regulation of NMDA receptor subunits and nitric oxide synthase expression during cocaine withdrawal. J Neurochem 75: 2040–2050, 2000.[CrossRef][Web of Science][Medline]

Nasif FJ, Hu XT, White FJ. Repeated cocaine administration increases voltage-sensitive calcium currents in response to membrane depolarization in medial prefrontal cortex pyramidal neurons. J Neurosci 25: 3674–3679, 2005.[Abstract/Free Full Text]

Neisewander JL, Baker DA, Fuchs RA, Tran-Nguyen LT, Palmer A, Marshall JF. Fos protein expression and cocaine-seeking behavior in rats after exposure to a cocaine self-administration environment. J Neurosci 20: 798–805, 2000.[Abstract/Free Full Text]

Nie Z, Schweitzer P, Roberts AJ, Madamba SG, Moore SD, Siggins GR. Ethanol augments GABAergic transmission in the central amygdala via CRF1 receptors. Science 303: 1512–1514, 2004.[Abstract/Free Full Text]

Pierce RC, Quick EA, Reeder DC, Morgan ZR, Kalivas PW. Calcium-mediated second messengers modulate the expression of behavioral sensitization to cocaine. J Pharmacol Exp Ther 286: 1171–1176, 1998.[Abstract/Free Full Text]

Pollandt S, Liu J, Orozco-Cabal L, Grigoriadis DE, Vale WW, Gallagher JP, Shinnick-Gallagher P. Cocaine withdrawal enhances long-term potentiation induced by corticotropin releasing factor (CRF) at central amygdala glutamatergic synapses via CRF₁ and PKA. Eur J Neurosci 24: 1733–1743, 2006.[CrossRef][Web of Science][Medline]

Radulovic J, Sydow S, Spiess J. Characterization of native corticotropin-releasing factor receptor type 1 (CRFR1) in the rat and mouse central nervous system. J Neurosci Res 54: 507–521, 1998.[CrossRef][Web of Science][Medline]

Reimer AR, Martin-Iverson MT. Nimodipine and haloperidol attenuate behavioural sensitization to cocaine but only nimodipine blocks the establishment of conditioned locomotion induced by cocaine. Psychopharmacology (Berl) 113: 404–410, 1994.[CrossRef][Medline]

Richter RM, Pich EM, Koob GF, Weiss F. Sensitization of cocaine-stimulated increase in extracellular levels of corticotropin-releasing factor from the rat amygdala after repeated administration as determined by intracranial microdialysis. Neurosci Lett 187: 169–172, 1995.[CrossRef][Web of Science][Medline]

Richter RM, Weiss F. In vivo CRF release in rat amygdala is increased during cocaine withdrawal in self-administering rats. Synapse 32: 254–261, 1999.[Web of Science][Medline]

Robinson TE, Berridge KC. The neural basis of drug craving: an incentive-sensitization theory of addiction. Brain Res Brain Res Rev 18: 247–291, 1993.[CrossRef][Medline]

Roozendaal B, Brunson KL, Holloway BL, McGaugh JL, Baram TZ. Involvement of stress-released corticotropin-releasing hormone in the basolateral amygdala in regulating memory consolidation. Proc Natl Acad Sci USA 99: 13908–13913, 2002.[Abstract/Free Full Text]

Sarnyai Z, Hohn J, Szabo G, Penke B. Critical role of endogenous corticotropin-releasing factor (CRF) in the mediation of the behavioral action of cocaine in rats. Life Sci 51: 2019–2024, 1992.[CrossRef][Web of Science][Medline]

Sarnyai Z, Shaham Y, Heinrichs SC. The role of corticotropin-releasing factor in drug addiction. Pharmacol Rev 53: 209–243, 2001.[Abstract/Free Full Text]

Shinnick-Gallagher P, Pitkanen A, Shekhar A, Cahill L. The Amygdala in Brain Function: Basic and Clinical Implications. New York: New York Academy of Sciences, 2003.

Thomas KL, Arroyo M, Everitt BJ. Induction of the learning and plasticity-associated gene Zif268 following exposure to a discrete cocaine-associated stimulus. Eur J Neurosci 17: 1964–1972, 2003.[CrossRef][Web of Science][Medline]

Thompson AM, Gosnell BA, Wagner JJ. Enhancement of long-term potentiation in the rat hippocampus following cocaine exposure. Neuropharmacology 42: 1039–1042, 2002.[CrossRef][Web of Science][Medline]

Thompson AM, Swant J, Gosnell BA, Wagner JJ. Modulation of long-term potentiation in the rat hippocampus following cocaine self-administration. Neuroscience 127: 177–185, 2004.[CrossRef][Web of Science][Medline]

Tian JB, Bishop GA. Frequency-dependent expression of corticotropin releasing factor in the rat's cerebellum. Neuroscience 121: 363–377, 2003.[CrossRef][Web of Science][Medline]

Turchan J, Maj M, Przewlocka B. The effect of drugs of abuse on NMDAR1 receptor expression in the rat limbic system. Drug Alcohol Depend 72: 193–196, 2003.[CrossRef][Web of Science][Medline]

Ungless MA, Singh V, Crowder TL, Yaka R, Ron D, Bonci A. Corticotropin-releasing factor requires CRF binding protein to potentiate NMDA receptors via CRF receptor 2 in dopamine neurons. Neuron 39: 401–407, 2003.[CrossRef][Web of Science][Medline]

Wang HL, Wayner MJ, Chai CY, Lee EH. Corticotrophin-releasing factor produces a long-lasting enhancement of synaptic efficacy in the hippocampus. Eur J Neurosci 10: 3428–3437, 1998.[CrossRef][Web of Science][Medline]

Zinebi F, Xie J, Liu J, Russell RT, Gallagher JP, McKernan MG, Shinnick-Gallagher P. NMDA currents and receptor protein are downregulated in the amygdala during maintenance of fear memory. J Neurosci 23: 10283–10291, 2003.[Abstract/Free Full Text]

Zorrilla EP, Valdez GR, Weiss F. Changes in levels of regional CRF-like-immunoreactivity and plasma corticosterone during protracted drug withdrawal in dependent rats. Psychopharmacology (Berl) 158: 374–381, 2001.[CrossRef][Medline]

This article has been cited by other articles:

				W. Francesconi, F. Berton, V. Repunte-Canonigo, K. Hagihara, D. Thurbon, D. Lekic, S. E. Specio, T. N. Greenwell, S. A. Chen, K. C. Rice, et al. Protracted Withdrawal from Alcohol and Drugs of Abuse Impairs Long-Term Potentiation of Intrinsic Excitability in the Juxtacapsular Bed Nucleus of the Stria Terminalis J. Neurosci., April 29, 2009; 29(17): 5389 - 5401. [Abstract] [Full Text] [PDF]

				T. L. Kash, W. P. Nobis, R. T. Matthews, and D. G. Winder Dopamine Enhances Fast Excitatory Synaptic Transmission in the Extended Amygdala by a CRF-R1-Dependent Process J. Neurosci., December 17, 2008; 28(51): 13856 - 13865. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) All Versions of this Article: 97/1/937    most recent 00349.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (6) Citing Articles via Google Scholar Google Scholar Articles by Fu, Y. Articles by Shinnick-Gallagher, P. Search for Related Content PubMed PubMed Citation Articles by Fu, Y. Articles by Shinnick-Gallagher, P.