Skip to main content

Advertisement

SpringerLink
Log in

Effect of β3 adrenoceptor activation in the basolateral amygdala on ethanol seeking behaviors

  • Original Investigation
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Rationale

The interaction between ethanol (EtOH) and anxiety plays an integral role in the development and maintenance of alcoholism. Many medications in pre-clinical or clinical trials for the treatment of alcoholism share anxiolytic properties. However, these drugs typically have untoward side effects, such as sedation or impairment of motor function that may limit their clinical use. We have recently demonstrated that BRL 37344 (BRL), a selective β3-adrenoceptor (AR) agonist, enhances a discrete population of GABAergic synapses in the basolateral amygdala (BLA) that mediates feed-forward inhibition from lateral paracapsular (LPC) GABAergic interneurons onto BLA pyramidal cells. Behavioral studies revealed that intra-BLA infusion of BRL significantly reduced measures of unconditioned anxiety-like behavior without locomotor depressant effects.

Objectives

The present studies tested the effect of BRL (0.1, 0.5, or 1.0 μg/side) on EtOH self-administration using an intermittent access home cage two-bottle choice procedure and limited access operant responding for EtOH or sucrose.

Results

Intra-BLA infusion of BRL did not reduce home cage, intermittent EtOH self-administration. However, using an operant procedure that permits the discrete assessment of appetitive (seeking) and consummatory measures of EtOH self-administration, BRL reduced measures of EtOH and sucrose seeking, but selectively reduced operant responding for EtOH during extinction probe trials. BRL had no effect on consummatory behaviors for EtOH or sucrose.

Conclusions

Together, these data suggest that intra-BLA infusion of BRL significantly reduces motivation to seek EtOH and provide initial evidence that β3-ARs and LPC GABAergic synapses may represent promising targets for the development of novel pharmacotherapies for the treatment of alcoholism.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  • Abraham PA, Xing G, Zhang L, Yu EZ, Post R, Gamble EH, Li H (2008) beta1- and beta2-adrenoceptor induced synaptic facilitation in rat basolateral amygdala. Brain Res 1209:65–73

    Article  CAS  PubMed  Google Scholar 

  • Ambroggi F, Ishikawa A, Fields HL, Nicola SM (2008) Basolateral amygdala neurons facilitate reward-seeking behavior by exciting nucleus accumbens neurons. Neuron 59:648–661

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Belujon P, Grace AA (2011) Hippocampus, amygdala, and stress: interacting systems that affect susceptibility to addiction. Ann N Y Acad Sci 1216:114–121

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Chappell AM, Carter E, McCool BA, Weiner JL (2013) Adolescent rearing conditions influence the relationship between initial anxiety-like behavior and ethanol drinking in male Long Evans rats. Alcohol Clin Exp Res 37(Suppl 1):E394–E403

    Article  PubMed  Google Scholar 

  • Chappell AM, Weiner JL (2008) Relationship between ethanol’s acute locomotor effects and ethanol self-administration in male Long-Evans rats. Alcohol Clin Exp Res 32:2088–2099

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Cheng HJ, Grant KA, Han QH, Daunais JB, Friedman DP, Masutani S, Little WC, Cheng CP (2010) Up-regulation and functional effect of cardiac beta3-adrenoreceptors in alcoholic monkeys. Alcohol Clin Exp Res 34:1171–1181

    CAS  PubMed Central  PubMed  Google Scholar 

  • Claustre Y, Leonetti M, Santucci V, Bougault I, Desvignes C, Rouquier L, Aubin N, Keane P, Busch S, Chen Y, Palejwala V, Tocci M, Yamdagni P, Didier M, Avenet P, Le Fur G, Oury-Donat F, Scatton B, Steinberg R (2008) Effects of the beta3-adrenoceptor (Adrb3) agonist SR58611A (amibegron) on serotonergic and noradrenergic transmission in the rodent: relevance to its antidepressant/anxiolytic-like profile. Neuroscience 156:353–364

    Article  CAS  PubMed  Google Scholar 

  • Clouse AK, Riedel E, Hieble JP, Westfall TD (2007) The effects and selectivity of beta-adrenoceptor agonists in rat myometrium and urinary bladder. Eur J Pharmacol 573:184–189

    Article  CAS  PubMed  Google Scholar 

  • Colombo G, Vacca G, Serra S, Brunetti G, Carai MA, Gessa GL (2003) Baclofen suppresses motivation to consume alcohol in rats. Psychopharmacology (Berl) 167:221–224

    CAS  Google Scholar 

  • Consoli D, Leggio GM, Mazzola C, Micale V, Drago F (2007) Behavioral effects of the beta3 adrenoceptor agonist SR58611A: is it the putative prototype of a new class of antidepressant/anxiolytic drugs? Eur J Pharmacol 573:139–147

    Article  CAS  PubMed  Google Scholar 

  • Czachowski CL, Delory MJ (2009) Acamprosate and naltrexone treatment effects on ethanol and sucrose seeking and intake in ethanol-dependent and nondependent rats. Psychopharmacology (Berl) 204:335–348

    Article  CAS  Google Scholar 

  • Fox HC, Anderson GM, Tuit K, Hansen J, Kimmerling A, Siedlarz KM, Morgan PT, Sinha R (2012) Prazosin effects on stress- and cue-induced craving and stress response in alcohol-dependent individuals: preliminary findings. Alcohol Clin Exp Res 36:351–360

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Funk CK, O’Dell LE, Crawford EF, Koob GF (2006) Corticotropin-releasing factor within the central nucleus of the amygdala mediates enhanced ethanol self-administration in withdrawn, ethanol-dependent rats. J Neurosci 26:11324–11332

    Article  CAS  PubMed  Google Scholar 

  • Gilpin NW, Misra K, Koob GF (2008) Neuropeptide Y in the central nucleus of the amygdala suppresses dependence-induced increases in alcohol drinking. Pharmacol, Biochem Behav 90:475–480

    Article  CAS  Google Scholar 

  • Hay RA, Jennings JH, Zitzman DL, Hodge CW, Robinson DL (2013) Specific and nonspecific effects of naltrexone on goal-directed and habitual models of alcohol seeking and drinking. Alcohol Clin Exp Res 37:1100–1110

    Google Scholar 

  • Kelley AE, Baldo BA, Pratt WE, Will MJ (2005) Corticostriatal-hypothalamic circuitry and food motivation: integration of energy, action and reward. Physiol Behav 86:773–795

    Article  CAS  PubMed  Google Scholar 

  • Koob GF (2009) Dynamics of neuronal circuits in addiction: reward, antireward, and emotional memory. Pharmacopsychiatry 42(Suppl 1):S32–S41

    Article  PubMed Central  PubMed  Google Scholar 

  • Koob GF (2011) Theoretical frameworks and mechanistic aspects of alcohol addiction: alcohol addiction as a reward deficit disorder. Curr Top Behav Neurosci 13:3–30

    Google Scholar 

  • Kushner MG, Abrams K, Thuras P, Hanson KL, Brekke M, Sletten S (2005) Follow-up study of anxiety disorder and alcohol dependence in comorbid alcoholism treatment patients. Alcohol Clin Exp Res 29:1432–1443

    Article  PubMed  Google Scholar 

  • Lack AK, Ariwodola OJ, Chappell AM, Weiner JL, McCool BA (2008) Ethanol inhibition of kainate receptor-mediated excitatory neurotransmission in the rat basolateral nucleus of the amygdala. Neuropharmacology 55:661–668

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Liebmann L, Karst H, Joels M (2009) Effects of corticosterone and the beta-agonist isoproterenol on glutamate receptor-mediated synaptic currents in the rat basolateral amygdala. Eur J Neurosci 30:800–807

    Article  PubMed  Google Scholar 

  • Marowsky A, Yanagawa Y, Obata K, Vogt KE (2005) A specialized subclass of interneurons mediates dopaminergic facilitation of amygdala function. Neuron 48:1025–1037

    Article  CAS  PubMed  Google Scholar 

  • McCool BA, Chappell A (2007) Strychnine and taurine modulation of amygdala-associated anxiety-like behavior is 'state' dependent. Behav Brain Res 178:70–81

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • McCool BA, Chappell AM (2009) Early social isolation in male Long-Evans rats alters both appetitive and consummatory behaviors expressed during operant ethanol self-administration. Alcohol Clin Exp Res 33:273–282

    Article  PubMed Central  PubMed  Google Scholar 

  • Menard J, Treit D (1999) Effects of centrally administered anxiolytic compounds in animal models of anxiety. Neurosci Biobehav Rev 23:591–613

    Article  CAS  PubMed  Google Scholar 

  • Myrick H, Anton RF, Li X, Henderson S, Randall PK, Voronin K (2008) Effect of naltrexone and ondansetron on alcohol cue-induced activation of the ventral striatum in alcohol-dependent people. Arch Gen Psychiatry 65:466–475

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Oriowo MA, Chapman H, Kirkham DM, Sennitt MV, Ruffolo RR Jr, Cawthorne MA (1996) The selectivity in vitro of the stereoisomers of the beta-3 adrenoceptor agonist BRL 37344. J Pharmacol Exp Ther 277:22–27

    CAS  PubMed  Google Scholar 

  • Paxinos G, Watson C (1997) The Rat Brain in Stereotaxic Coordinates, 4th ed. Academic Press: San Diego, CA

  • Rasmussen DD, Alexander LL, Raskind MA, Froehlich JC (2009) The alpha1-adrenergic receptor antagonist, prazosin, reduces alcohol drinking in alcohol-preferring (P) rats. Alcohol Clin Exp Res 33:264–272

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Rodriguez M, Carillon C, Coquerel A, Le Fur G, Ferrara P, Caput D, Shire D (1995) Evidence for the presence of beta 3-adrenergic receptor mRNA in the human brain. Brain Res Mol Brain Res 29:369–375

    Article  CAS  PubMed  Google Scholar 

  • Sabino V, Cottone P, Blasio A, Iyer MR, Steardo L, Rice KC, Conti B, Koob GF, Zorrilla EP (2011) Activation of sigma-receptors induces binge-like drinking in Sardinian alcohol-preferring rats. Neuropsychopharmacology 36:1207–1218

    Article  CAS  PubMed  Google Scholar 

  • Samson HH (1986) Initiation of ethanol reinforcement using a sucrose-substitution procedure in food- and water-sated rats. Alcohol Clin Exp Res 10:436–442

    Article  CAS  PubMed  Google Scholar 

  • Samson HH, Chappell AM (2004) Effects of raclopride in the core of the nucleus accumbens on ethanol seeking and consumption: the use of extinction trials to measure seeking. Alcohol Clin Exp Res 28:544–549

    Article  CAS  PubMed  Google Scholar 

  • Samson HH, Czachowski CL (2003) Behavioral measures of alcohol self-administration and intake control: rodent models. Int Rev Neurobiol 54:107–143

    PubMed  Google Scholar 

  • Samson HH, Czachowski CL, Chappell A, Legg B (2003) Measuring the appetitive strength of ethanol: use of an extinction trial procedure. Alcohol 31:77–86

    Article  CAS  PubMed  Google Scholar 

  • Samson HH, Czachowski CL, Slawecki CJ (2000) A new assessment of the ability of oral ethanol to function as a reinforcing stimulus. Alcohol Clin Exp Res 24:766–773

    Article  CAS  PubMed  Google Scholar 

  • Samson HH, Sharpe AL, Denning C (1999) Initiation of ethanol self-administration in the rat using sucrose substitution in a sipper-tube procedure. Psychopharmacology (Berl) 147:274–279

    Article  CAS  Google Scholar 

  • Samson HH, Slawecki CJ, Sharpe AL, Chappell A (1998) Appetitive and consummatory behaviors in the control of ethanol consumption: a measure of ethanol seeking behavior. Alcohol Clin Exp Res 22:1783–1787

    CAS  PubMed  Google Scholar 

  • Silberman Y, Ariwodola OJ, Chappell AM, Yorgason JT, Weiner JL (2010) Lateral paracapsular GABAergic synapses in the basolateral amygdala contribute to the anxiolytic effects of beta 3 adrenoceptor activation. Neuropsychopharmacology 35:1886–1896

    Article  CAS  PubMed  Google Scholar 

  • Silberman Y, Shi L, Brunso-Bechtold JK, Weiner JL (2008) Distinct mechanisms of ethanol potentiation of local and paracapsular GABAergic synapses in the rat basolateral amygdala. J Pharmacol Exp Ther 324:251–260

    Article  CAS  PubMed  Google Scholar 

  • Simms JA, Steensland P, Medina B, Abernathy KE, Chandler LJ, Wise R, Bartlett SE (2008) Intermittent access to 20% ethanol induces high ethanol consumption in Long-Evans and Wistar rats. Alcohol Clin Exp Res 32:1816–1823

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Stemmelin J, Cohen C, Terranova JP, Lopez-Grancha M, Pichat P, Bergis O, Decobert M, Santucci V, Francon D, Alonso R, Stahl SM, Keane P, Avenet P, Scatton B, le Fur G, Griebel G (2008) Stimulation of the beta3-Adrenoceptor as a novel treatment strategy for anxiety and depressive disorders. Neuropsychopharmacology 33:574–587

    Article  CAS  PubMed  Google Scholar 

  • Stuber GD, Sparta DR, Stamatakis AM, van Leeuwen WA, Hardjoprajitno JE, Cho S, Tye KM, Kempadoo KA, Zhang F, Deisseroth K, Bonci A (2011) Excitatory transmission from the amygdala to nucleus accumbens facilitates reward seeking. Nat Geosci 475:377–380

    CAS  Google Scholar 

  • Summers RJ, Papaioannou M, Harris S, Evans BA (1995) Expression of beta 3-adrenoceptor mRNA in rat brain. Br J Pharmacol 116:2547–2548

    Article  CAS  PubMed  Google Scholar 

  • Tamburella A, Micale V, Leggio GM, Drago F (2010) The beta3 adrenoceptor agonist, amibegron (SR58611A) counteracts stress-induced behavioral and neurochemical changes. Eur Neuropsychopharmacol 20:704–713

    Article  CAS  PubMed  Google Scholar 

  • Tye KM, Stuber GD, de Ridder B, Bonci A, Janak PH (2008) Rapid strengthening of thalamo-amygdala synapses mediates cue-reward learning. Nat Geosci 453:1253–1257

    CAS  Google Scholar 

  • Verplaetse TL, Rasmussen DD, Froehlich JC, Czachowski CL (2011) Effects of prazosin, an alpha(1)-adrenergic receptor antagonist, on the seeking and intake of alcohol and sucrose in alcohol-preferring (P) rats. Alcohol Clin Exp Res 36(5):881–886

    Google Scholar 

  • Walker BM, Rasmussen DD, Raskind MA, Koob GF (2008) alpha1-noradrenergic receptor antagonism blocks dependence-induced increases in responding for ethanol. Alcohol 42:91–97

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Wise RA (1973) Voluntary ethanol intake in rats following exposure to ethanol on various schedules. Psychopharmacologia 29:203–210

    Article  CAS  PubMed  Google Scholar 

  • Yorgason JT, Espana RA, Konstantopoulos JK, Weiner JL, Jones SR (2013) Enduring increases in anxiety-like behavior and rapid nucleus accumbens dopamine signaling in socially isolated rats. Eur J Neurosci 37:1022–1031

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by the National Institutes of Health grants AA 21099, AA 17056, AA 17531, and AA 10422 and T32 AA 7565.

Author information

Authors and Affiliations

  1. Department of Physiology and Pharmacology, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC, 27157, USA

    T. R. Butler, A. M. Chappell & J. L. Weiner

Authors
  1. T. R. Butler
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. M. Chappell
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J. L. Weiner
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to J. L. Weiner.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Butler, T.R., Chappell, A.M. & Weiner, J.L. Effect of β3 adrenoceptor activation in the basolateral amygdala on ethanol seeking behaviors. Psychopharmacology 231, 293–303 (2014). https://doi.org/10.1007/s00213-013-3238-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-013-3238-y

Keywords

Search

Navigation