title: Inhibition of hippocampal β-adrenergic receptors impairs retrieval but not reconsolidation of cocaine-associated memory and prevents subsequent reinstatement.
abstract: Retrieval of drug-associated memories is critical for maintaining addictive behaviors, as presentation of drug-associated cues can elicit drug seeking and relapse. Recently, we and others have demonstrated that β-adrenergic receptor (β-AR) activation is necessary for retrieval using both rat and human memory models. Importantly, blocking retrieval with β-AR antagonists persistently impairs retrieval and provides protection against subsequent reinstatement. However, the neural locus at which β-ARs are required for maintaining retrieval and subsequent reinstatement is unclear. Here, we investigated the necessity of dorsal hippocampus (dHipp) β-ARs for drug-associated memory retrieval. Using a cocaine conditioned place preference (CPP) model, we demonstrate that local dHipp β-AR blockade before a CPP test prevents CPP expression shortly and long after treatment, indicating that dHipp β-AR blockade induces a memory retrieval disruption. Furthermore, this retrieval disruption provides long-lasting protection against cocaine-induced reinstatement. The effects of β-AR blockade were dependent on memory reactivation and were not attributable to reconsolidation disruption as blockade of β-ARs immediately after a CPP test had little effect on subsequent CPP expression. Thus, cocaine-associated memory retrieval is mediated by β-AR activity within the dHipp, and disruption of this activity could prevent cue-induced drug seeking and relapse long after treatment.
authors.affiliation: Department of Psychology, University of Wisconsin-Milwaukee, Milwaukee, WI, USA.
authors.forename: James M
authors.initials: JM
authors.lastname: Otis
authors.affiliation: Department of Psychology, University of Wisconsin-Milwaukee, Milwaukee, WI, USA.
authors.forename: Michael K
authors.initials: MK
authors.lastname: Fitzgerald
authors.affiliation: Department of Psychology, University of Wisconsin-Milwaukee, Milwaukee, WI, USA.
authors.forename: Devin
authors.initials: D
authors.lastname: Mueller
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001245:Association Learning / Q000187:drug effects* / Q000502:physiology; D003042:Cocaine / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008568:Memory / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D020318:Rats, Long-Evans; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*
chemical_list: D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta; D003042:Cocaine
references.citation: Alcohol Clin Exp Res. 2006 Aug;30(8):1349-54
references.pmid: 16899037
references.citation: Neuropsychopharmacology. 2011 Aug;36(9):1912-20
references.pmid: 21544069
references.citation: Learn Mem. 2009 Nov 25;16(12):777-89
references.pmid: 19940038
references.citation: Cell. 2004 Apr 2;117(1):131-43
references.pmid: 15066288
references.citation: Psychiatr Clin North Am. 1986 Sep;9(3):413-25
references.pmid: 3534813
references.citation: Learn Mem. 2004 Sep-Oct;11(5):501-9
references.pmid: 15466300
references.citation: J Neurosci. 2010 Jul 14;30(28):9631-40
references.pmid: 20631192
references.citation: J Neurosci. 2004 Aug 4;24(31):6889-97
references.pmid: 15295023
references.citation: Science. 2004 May 7;304(5672):839-43
references.pmid: 15073322
references.citation: Neuron. 1993 Dec;11(6):1023-35
references.pmid: 8274274
references.citation: Prog Brain Res. 1991;88:571-85
references.pmid: 1813935
references.citation: Med Pharmacol Exp Int J Exp Med. 1967;16(4):343-9
references.pmid: 4384498
references.citation: Learn Mem. 2011 Oct 17;18(11):693-702
references.pmid: 22005750
references.citation: Learn Mem. 2010 Mar 23;17(4):168-75
references.pmid: 20332188
references.citation: Nat Rev Neurosci. 2009 Mar;10(3):211-23
references.pmid: 19190638
references.citation: J Neurosci. 2013 Jan 16;33(3):1271-81a
references.pmid: 23325262
references.citation: Behav Neurosci. 2006 Apr;120(2):401-12
references.pmid: 16719704
references.citation: Neuron. 2002 Oct 24;36(3):527-38
references.pmid: 12408854
references.citation: Behav Brain Res. 1991 Apr 18;43(1):93-7
references.pmid: 1650233
references.citation: Science. 1992 May 1;256(5057):675-7
references.pmid: 1585183
references.citation: Psychopharmacology (Berl). 2012 May;221(1):19-26
references.pmid: 22048130
references.citation: Neuroscience. 2010 Oct 13;170(2):570-9
references.pmid: 20654701
references.citation: Behav Brain Res. 2000 Oct;115(1):39-47
references.pmid: 10996406
references.citation: PLoS One. 2011;6(10):e26220
references.pmid: 22022574
references.citation: Science. 2000 Jan 14;287(5451):248-51
references.pmid: 10634773
references.citation: Eur J Neurosci. 2009 Sep;30(5):901-12
references.pmid: 19712098
references.citation: Neuropsychopharmacology. 2005 Feb;30(2):296-309
references.pmid: 15483559
references.citation: Cereb Cortex. 2008 Jul;18(7):1506-20
references.pmid: 17965126
references.citation: Science. 1980 Sep 5;209(4461):1138-40
references.pmid: 7403874
references.citation: Neuroscience. 1997 Oct;80(3):697-715
references.pmid: 9276487
references.citation: J Neurosci. 2010 Mar 17;30(11):3959-63
references.pmid: 20237266
references.citation: Science. 2006 Feb 17;311(5763):1017-20
references.pmid: 16484499
references.citation: Addiction. 1998 May;93(5):713-27
references.pmid: 9692270
references.citation: Drug Alcohol Depend. 2006 Nov 8;85(2):129-37
references.pmid: 16697124
references.citation: Ann Neurosci. 2010 Jul;17(3):136-41
references.pmid: 25205891
references.citation: Vascul Pharmacol. 2006 Oct;45(4):243-50
references.pmid: 16899413
references.citation: Neuroreport. 2007 Jul 16;18(11):1107-11
references.pmid: 17589308
references.citation: Science. 1984 Oct 19;226(4672):350-2
references.pmid: 6091272
references.citation: Front Behav Neurosci. 2010 Nov 26;4:179
references.pmid: 21152256
references.citation: Psychopharmacology (Berl). 2000 Mar;149(1):24-33
references.pmid: 10789879
references.citation: Neuroreport. 2003 Nov 14;14(16):2127-31
references.pmid: 14600510
references.citation: J Neurosci. 2001 Mar 1;21(5):1720-6
references.pmid: 11222661
references.citation: J Neurosci. 2008 Jan 9;28(2):369-75
references.pmid: 18184779
references.citation: Neuropsychopharmacology. 2010 Feb;35(3):720-6
references.pmid: 19890257
references.citation: J Neurosci. 2000 Jan 15;20(2):798-805
references.pmid: 10632609
references.citation: Drug Alcohol Depend. 2001 Jun 1;63(1):69-78
references.pmid: 11297832