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Effects of lidocaine-induced inactivation of the bed nucleus of the stria terminalis, the central or the basolateral nucleus of the amygdala on the opponent-process actions of self-administered cocaine in rats

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Abstract

Rationale

In addition to its rewarding actions, cocaine has profound negative effects that are unmasked as the rewarding impact of the drug fades. While much is known about the neurobiology of cocaine reward, the mechanisms underlying the negative actions of the drug remain unclear.

Objectives

The current study investigates the role of three brain regions each implicated in the modulation of negative affective states—the bed nucleus of the stria terminalis (BNST), the central (CeA), and the basolateral (BLA) nucleus of the amygdala.

Methods

The dual actions of cocaine were assessed using a runway self-administration procedure in which rats exhibit both approach to and avoidance of a goal box associated with cocaine administration (retreat behaviors). Here, rats ran a straight alley once/day for i.v. cocaine (1.0 mg/kg/injection) over 14 days during which the BNST, CeA, or BLA was inactivated via bilateral intracranial infusions of lidocaine (0 or 20 μg/0.5 μl/side) administered 15 min prior to testing. The impact of lidocaine on spontaneous locomotor activity was also assessed to rule out nonspecific actions of the treatments.

Results

Control animals running for cocaine developed the expected pattern of approach–avoidance retreat behavior. Inactivation of the BNST attenuated such behavior, BLA inactivation had no appreciable effects, and CeA inactivation produced intermediate and more variable results. Locomotor activity was unaffected by any of the treatments.

Conclusions

These data suggest that the BNST and to a lesser extent the CeA, but not the BLA, play a role in mediating the opponent-process actions of self-administered cocaine.

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References

  • Ambrosio E, Sharpe LG, Pilotte NS (1997) Regional binding to corticotropin releasing factor receptors in brain of rats exposed to chronic cocaine and cocaine withdrawal. Synapse 25(3):272–276

    Article  PubMed  CAS  Google Scholar 

  • Anthony JC, Tien AY, Petronis KR (1989) Epidemiologic evidence on cocaine use and panic attacks. Am J Epidemiol 129(3):543–549

    PubMed  CAS  Google Scholar 

  • Asan E (1998) The catecholaminergic innervation of the rat amygdala. Adv Anat Embryol Cell Biol 142:L1–L118

    Google Scholar 

  • Blanchard RJ, Kaawaloa JN, Hebert MA, Blanchard DC (1999) Cocaine produces panic-like flight responses in mice in the mouse defense test battery. Pharmacol Biochem Behav 64(3):523–528

    Article  PubMed  CAS  Google Scholar 

  • Buffalari DM, See RE (2010) Inactivation of the bed nucleus of the stria terminalis in an animal model of relapse: effects on conditioned cue-induced reinstatement and its enhancement by yohimbine. Psychopharmacology (Berl) 213(1):19–27

    Article  Google Scholar 

  • Catterall WA (1980) Neurotoxins that act on voltage-sensitive sodium channels in excitable membranes. Ann Rev Pharmacol Toxicol 20:15–43

    Article  CAS  Google Scholar 

  • Cohen A, Young RW, Velazquez MA, Groysman M, Noorbehesht K, Ben-Shahar O, Ettenberg A (2009) Anxiolytic effects of nicotine in a rodent test of approach–avoidance conflict. Psychopharmacology 204(3):541–549

    Article  PubMed  CAS  Google Scholar 

  • Corominas M, Roncero C, Casas M (2010) Corticotropin releasing factor and neuroplasticity in cocaine addiction. Life Sci 86:1–9

    Article  PubMed  CAS  Google Scholar 

  • Davis M (2006) Neural systems involved in fear and anxiety measured with fear-potentiated startle. Am Psychol 61(8):741–756

    Article  PubMed  Google Scholar 

  • Davis M, Shi C (1999) The extended amygdala: are the central nucleus of the amygdala and the bed nucleus of the stria terminalis differentially involved in fear versus anxiety? Ann N Y Acad Sci 877:281–291

    Article  PubMed  CAS  Google Scholar 

  • Davis M, Walker DL, Miles L, Grillon C (2010) Phasic vs sustained fear in rats and humans: role of the extended amygdala in fear vs anxiety. Neuropsychopharmacology 35:105–135

    Article  PubMed  Google Scholar 

  • De la Mora MP, Gallegos-Cari A, Arizmendi-García Y, Marcellino D, Fuxe K (2010) Role of dopamine receptor mechanisms in the amygdaloid modulation of fear and anxiety: structural and functional analysis. Prog Neurobiol 90:198–216

    Article  PubMed  Google Scholar 

  • Erb S (2010) Evaluation of the relationship between anxiety during withdrawal and stress-induced reinstatement of cocaine seeking. Prog Neuropsychopharmacol Biol Psychiatry 34(5):798–807

    Article  PubMed  CAS  Google Scholar 

  • Erb S, Stewart J (1999) A role for the bed nucleus of the stria terminalis, but not the amygdala, in the effects of corticotropin-releasing factor on stress-induced reinstatement of cocaine seeking. J Neurosci 19(20):RC35

    PubMed  CAS  Google Scholar 

  • Erb S, Salmaso N, Rodaros D, Stewart J (2001) A role for the CRF-containing pathway from central nucleus of the amygdala to bed nucleus of the stria terminalis in the stress-induced reinstatement of cocaine seeking in rats. Psychopharmacology 158(4):360–365

    Article  PubMed  CAS  Google Scholar 

  • Erb S, Funk D, Borkowski S, Watson SJ, Akil H (2004) Effects of chronic cocaine exposure on corticotropin-releasing hormone binding protein in the central nucleus of the amygdala and bed nucleus of the stria terminalis. Neuroscience 123(4):1003–1009

    Article  PubMed  CAS  Google Scholar 

  • Ettenberg A (2004) Opponent process properties of self-administered cocaine. Neurosci Biobehav Rev 27(8):721–728

    Article  PubMed  CAS  Google Scholar 

  • Ettenberg A (2009) The runway model of drug self-administration. Pharmacol Biochem Behav 91:271–277

    Article  PubMed  CAS  Google Scholar 

  • Ettenberg A, Bernardi RE (2006) Anxiolytic-like actions of buspirone in a runway model of intravenous cocaine self-administration. Pharmacol Biochem Behav 85:393–399

    Article  PubMed  CAS  Google Scholar 

  • Ettenberg A, Bernardi RE (2007) Effects of buspirone on the immediate positive and delayed negative properties of intravenous cocaine as measured in the conditioned place preference test. Pharmacol Biochem Behav 87:171–178

    Article  PubMed  CAS  Google Scholar 

  • Ettenberg A, Geist TD (1991) Animal model for investigating the anxiogenic effects of self-administered cocaine. Psychopharmacology 103(4):455–461

    Article  PubMed  CAS  Google Scholar 

  • Ettenberg A, Geist TD (1993) Qualitative and quantitative differences in the operant runway behavior of rats working for cocaine and heroin reinforcement. Pharmacol Biochem Behav 44:191–198

    Article  PubMed  CAS  Google Scholar 

  • Ettenberg A, Raven MA, Danluck DA, Necessary BD (1999) Evidence for opponent-process actions of intravenous cocaine. Pharmacol Biochem Behav 64:507–512

    Article  PubMed  CAS  Google Scholar 

  • Forray MI, Bustos G, Gysling K (1997) Regulation of norepinephrine release from the rat bed nucleus of the stria terminalis: in vivo microdialysis studies. J Neurosci Res 50:1040–1046

    Article  PubMed  CAS  Google Scholar 

  • Freedman LJ, Cassell MD (1994) Distribution of dopaminergic fibers in the central division of the extended amygdala of the rat. Brain Res 633:243–252

    Article  PubMed  CAS  Google Scholar 

  • Gabriele A, See RE (2010) Reversible inactivation of the basolateral amygdala, but not the dorsolateral caudate putamen, attenuates consolidation of cocaine-cue associative learning in a reinstatement model of drug-seeking. Eur J Neurosci 32(6):1024–1029

    Article  PubMed  Google Scholar 

  • Geist TD, Ettenberg A (1990) A simple method for studying intravenous drug reinforcement in a runaway. Pharmacol Biochem Behav 36:703–706

    Article  PubMed  CAS  Google Scholar 

  • Geist TD, Ettenberg A (1997) Concurrent positive and negative goal-box events produce runway behaviors comparable to those of cocaine-reinforced rats. Pharmacol Biochem Behav 57:145–150

    Article  PubMed  CAS  Google Scholar 

  • Goeders NE, McNulty MA, Guerin GF (1993) Effects of alprazolam on intravenous cocaine self-administration in rats. Pharmacol Biochem Behav 44:471–474

    Article  PubMed  CAS  Google Scholar 

  • Guzman D, Ettenberg A (2007) Runway self-administration of intracerebroventricular cocaine: evidence of mixed positive and negative drug actions. Behav Pharmacol 18(1):53–60

    Article  PubMed  CAS  Google Scholar 

  • Hale MW, Hay-Schmidt A, Mikkelsen JD, Poulsen B, Shekhar A, Lowry CA (2008) Exposure to an open-field arena increases c-Fos expression in a distributed anxiety-related system projecting to the basolateral amygdaloid complex. Neuroscience 155:659–672

    Article  PubMed  CAS  Google Scholar 

  • Kantak KM, Black Y, Valencia E, Green-Jordan K, Eichenbaum HB (2002) Dissociable effects of lidocaine inactivation of the rostral and caudal basolateral amygdala on the maintenance and reinstatement of cocaine-seeking behavior in rats. Neuroscience 22:1126–1136

    PubMed  CAS  Google Scholar 

  • Knackstedt LA, Ettenberg A (2005) Ethanol consumption reduces the adverse consequences of self-administered intravenous cocaine in rats. Psychopharmacology 178(2–3):143–150

    Article  PubMed  CAS  Google Scholar 

  • Knackstedt LA, Samimi MM, Ettenberg A (2002) Evidence for opponent-process actions of intravenous cocaine and cocaethylene. Pharmacol Biochem Behav 72:931–936

    Article  PubMed  CAS  Google Scholar 

  • Koob GF (1999) Corticotropin-releasing factor, norepinephrine, and stress. Biol Psychiatry 46:1167–1180

    Article  PubMed  CAS  Google Scholar 

  • Koob GF (2008) Hedonic homeostatic dysregulation as a driver of drug-seeking behavior. Drug Discov Today Dis Models 5(4):207–215

    Article  PubMed  Google Scholar 

  • Leri F, Flores J, Rodaros D, Stewart J (2002) Blockade of stress-induced but not cocaine-induced reinstatement by infusion of noradrenergic antagonists into the bed nucleus of the stria terminalis or the central nucleus of the amygdala. J Neurosci 22:5713–5718

    PubMed  CAS  Google Scholar 

  • Liang KC, Chen HC, Chen DY (2001) Posttraining infusion of norepinephrine and corticotropin releasing factor into the bed nucleus of the stria terminalis enhanced retention in an inhibitory avoidance task. Chin J Physiol 44:33–43, Erratum in Chin J Physiol 44:151

    PubMed  CAS  Google Scholar 

  • Lomber SG (1999) The advantages and limitations of permanent or reversible deactivation techniques in the assessment of neural function. J Neurosci Methods 86:109–117

    Article  PubMed  CAS  Google Scholar 

  • Maier E, Ledesma RT, Seiwell AP, Duvauchelle CL (2008) Diazepam alters cocaine self-administration, but not cocaine-stimulated locomotion or nucleus accumbens dopamine. Pharmacol Biochem Behav 91:202–207

    Article  PubMed  CAS  Google Scholar 

  • Mello NK, Mendelson JH (1997) Cocaine’s effects on neuroendocrine systems: clinical and preclinical studies. Pharmacol Biochem Behav 57:571–599

    Article  PubMed  CAS  Google Scholar 

  • Miller NE (1944) Experimental studies of conflict. In: Hunt J McV (ed) Personality and behavior disorders. The Ronald Press Company, New York, pp 431–465

    Google Scholar 

  • Nakagawa T, Yamamoto R, Fujio M, Suzuki Y, Minami M, Satoh M, Kaneko S (2005) Involvement of the bed nucleus of the stria terminalis activated by the central nucleus of the amygdala in the negative affective component of morphine withdrawal in rats. Neuroscience 134(1):9–19

    Article  PubMed  CAS  Google Scholar 

  • Paxinos G, Watson C (1998) The rat brain in stereotaxic coordinates, 5th edn. Academic Press, New York

    Google Scholar 

  • Phelix CF, Liposits Z, Paull WK (1994) Catecholamine-CRF synaptic interaction in a septal bed nucleus: afferents of neurons in the bed nucleus of the stria terminalis. Brain Res Bull 33:109–119

    Article  PubMed  CAS  Google Scholar 

  • Raven MA, Necessary BD, Danluck DA, Ettenberg A (2000) Comparison of the reinforcing and anxiogenic effects of intravenous cocaine and cocaethylene. Exp Clin Psychopharmacol 8:117–124

    Article  PubMed  CAS  Google Scholar 

  • Resnick RB, Kestenbaum RS, Schwartz LK (1977) Acute systemic effects of cocaine in man: a controlled study by intranasal and intravenous routes. Science 195:696–698

    Article  PubMed  CAS  Google Scholar 

  • Resstel LB, Alves FH, Reis DG, Crestani CC, Corrêa FM, Guimarães FS (2008) Anxiolytic-like effects induced by acute reversible inactivation of the bed nucleus of stria terminalis. Neuroscience 154:869–876

    Article  PubMed  CAS  Google Scholar 

  • Richelson E, Pfenning M (1984) Blockade by antidepressants and related compounds of biogenic amine uptake into rat brain synaptosomes: most antidepressants selectively block norepinephrine uptake. Eur J Pharmacol 104:277–286

    Article  PubMed  CAS  Google Scholar 

  • Richter RM, Weiss F (1999) In vivo CRF release in rat amygdala is increased during cocaine withdrawal in self-administering rats. Synapse 32:254–261

    PubMed  CAS  Google Scholar 

  • Rogerio R, Takahashi RN (1992) Anxiogenic properties of cocaine in the rat evaluated with the elevated plus-maze. Pharmacol Biochem Behav 43:631–633

    Article  PubMed  CAS  Google Scholar 

  • Rohsenow DJ, Martin RA, Eaton CA, Monti PM (2007) Cocaine craving as a predictor of treatment attrition and outcomes after residential treatment for cocaine dependence. J Stud Alcohol Drugs 68:641–648

    PubMed  Google Scholar 

  • Rothman RB, Baumann MH, Dersch CM, Romero DV, Rice KC, Carroll FI, Partilla JS (2001) Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin. Synapse 39:32–41

    Article  PubMed  CAS  Google Scholar 

  • Sakanaka M, Shibasaki T, Lederis K (1986) Distribution and efferent projections of corticotropin-releasing factor-like immunoreactivity in the rat amygdaloid complex. Brain Res 382:213–238

    Article  PubMed  CAS  Google Scholar 

  • Sarnyai Z, Bíró E, Gardi J, Vecsernyés M, Julesz J, Telegdy G (1995) Brain corticotropin-releasing factor mediates ‘anxiety-like’ behavior induced by cocaine withdrawal in rats. Brain Res 675:89–97

    Article  PubMed  CAS  Google Scholar 

  • Shaham Y, Shalev U, Lu L, De Wit H, Stewart J (2003) The reinstatement model of drug relapse: history, methodology and major findings. Psychopharmacology 168:3–20

    Article  PubMed  CAS  Google Scholar 

  • Smith RJ, Aston-Jones G (2008) Noradrenergic transmission in the extended amygdala: role in increased drug-seeking and relapse during protracted drug abstinence. Brain Struct Funct 213:43–61

    Article  PubMed  Google Scholar 

  • Sullivan GM, Apergis J, Bush DE, Johnson LR, Hou M, Ledoux JE (2004) Lesions in the bed nucleus of the stria terminalis disrupt corticosterone and freezing responses elicited by a contextual but not by a specific cue-conditioned fear stimulus. Neuroscience 128:7–14

    Article  PubMed  CAS  Google Scholar 

  • Tanimoto S, Nakagawa T, Yamauchi Y, Minami M, Satoh M (2003) Differential contributions of the basolateral and central nuclei of the amygdala in the negative affective component of chemical somatic and visceral pains in rats. Eur J Neurosci 18:2343–2350

    Article  PubMed  Google Scholar 

  • Tehovnik EJ, Sommer MA (1997) Effective spread and timecourse of neural inactivation caused by lidocaine injection in monkey cerebral cortex. J Neurosci Methods 74:17–26

    Article  PubMed  CAS  Google Scholar 

  • Théberge FR, Milton AL, Belin D, Lee JL, Everitt BJ (2010) The basolateral amygdala and nucleus accumbens core mediate dissociable aspects of drug memory reconsolidation. Learn Mem 17:444–453

    Article  PubMed  Google Scholar 

  • Treit D, Aujla H, Menard J (1998) Does the bed nucleus of the stria terminalis mediate fear behaviors? Behav Neurosci 112:379–386

    Article  PubMed  CAS  Google Scholar 

  • Tsagarakis S, Holly JM, Rees LH, Besser GM, Grossman A (1988) Acetylcholine and norepinephrine stimulate the release of corticotropin-releasing factor-41 from the rat hypothalamus in vitro. Endocrinology 123(4):1962–1969

    Article  PubMed  CAS  Google Scholar 

  • Waddell J, Morris RW, Bouton ME (2006) Effects of bed nucleus of the stria terminalis lesions on conditioned anxiety: aversive conditioning with long-duration conditional stimuli and reinstatement of extinguished fear. Behav Neurosci 120:324–336

    Article  PubMed  Google Scholar 

  • Wakonigg G, Sturm K, Saria A, Zernig G (2003) Opioids, cocaine, and food change runtime distribution in a rat runway procedure. Psychopharmacology 169:52–59

    Article  PubMed  CAS  Google Scholar 

  • Walker DL, Davis M (2008) Role of the extended amygdala in short-duration versus sustained fear: a tribute to Dr. Lennart Heimer. Brain Struct Funct 213:29–42

    Article  PubMed  Google Scholar 

  • Walker DL, Toufexis DJ, Davis M (2003) Role of the bed nucleus of the stria terminalis versus the amygdala in fear, stress, and anxiety. Eur J Pharmacol 463:199–216

    Article  PubMed  CAS  Google Scholar 

  • Waraczynski M (2003) Lidocaine inactivation demonstrates a stronger role for central versus medial extended amygdala in medial forebrain bundle self-stimulation. Brain Res 962:180–198

    Article  PubMed  CAS  Google Scholar 

  • Watanabe T, Yamamoto R, Maeda A, Nakagawa T, Minami M, Satoh M (2002) Effects of excitotoxic lesions of the central or basolateral nucleus of the amygdala on naloxone-precipitated withdrawal-induced conditioned place aversion in morphine-dependent rats. Brain Res 958:423–428

    Article  PubMed  CAS  Google Scholar 

  • Williamson S, Gossop M, Powis B, Griffiths P, Fountain J, Strang J (1997) Adverse effects of stimulant drugs in a community sample of drug users. Drug Alcohol Depend 44:87–94

    Article  PubMed  CAS  Google Scholar 

  • Woods VE, Ettenberg A (2004) Increased amphetamine-induced locomotion during inactivation of the basolateral amygdala. Behav Brain Res 149:33–39

    Article  PubMed  CAS  Google Scholar 

  • Yang XM, Gorman AL, Dunn AJ, Goeders NE (1992) Anxiogenic effects of acute and chronic cocaine administration: neurochemical and behavioral studies. Pharmacol Biochem Behav 41:643–650

    Article  PubMed  CAS  Google Scholar 

  • Young AM, Rees KR (1998) Dopamine release in the amygdaloid complex of the rat, studied by brain microdialysis. Neurosci Lett 249:49–52

    Article  PubMed  CAS  Google Scholar 

  • Zernig G, Ahmed SH, Cardinal RN, Morgan D, Acquas E, Foltin RW, Vezina P, Negus SS, Crespo JA, Stöckl P, Grubinger P, Madlung E, Haring C, Kurz M, Saria A (2007) Explaining the escalation of drug use in substance dependence: models and appropriate animal laboratory tests. Pharmacology 80:65–119

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This research was supported by grant DA05041 from the National Institute of Drug Abuse awarded to AE. The authors wish to thank Dr. Skirmantas Janusonis for the assistance with creating the histological photomicrographs.

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Authors and Affiliations

  1. Behavioral Pharmacology Laboratory, Department of Psychology, University of California, Santa Barbara, Santa Barbara, CA, 93106–9660, USA

    Jennifer M. Wenzel, Stephanie A. Waldroup, Zachary M. Haber, Zu-In Su, Osnat Ben-Shahar & Aaron Ettenberg

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  1. Jennifer M. Wenzel
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  2. Stephanie A. Waldroup
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  3. Zachary M. Haber
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Correspondence to Aaron Ettenberg.

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Wenzel, J.M., Waldroup, S.A., Haber, Z.M. et al. Effects of lidocaine-induced inactivation of the bed nucleus of the stria terminalis, the central or the basolateral nucleus of the amygdala on the opponent-process actions of self-administered cocaine in rats. Psychopharmacology 217, 221–230 (2011). https://doi.org/10.1007/s00213-011-2267-7

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