Alternation in dopamine D 2 -like and metabotropic glutamate type 5 receptor density caused by differing housing conditions during abstinence from cocaine self-administration in rats

Abstract

Background:

Environmental conditions have an important function in substance use disorder, increasing or decreasing the risks of relapse. Several studies strongly support the role of the dopamine D₂-like and metabotropic glutamate type 5 receptors in maladaptive neurobiological responses to cocaine reward and relapse.

Aims:

The present study employed cocaine self-administration with yoked-triad procedure in rats to explore whether drug abstinence in different housing conditions affects the drug-seeking behaviour and the dopamine D₂-like and metabotropic glutamate type 5 receptor density and affinity in several regions of the animal brain.

Methods:

Rats were trained to self-administer cocaine and later they were forced to abstain either in: (a) enriched environment or (b) isolation cage conditions to evaluate the effect of housing conditions on the drug-seeking behaviour and to assess changes concerning receptors in animals brain.

Results:

Our results show that exposure to enriched environment conditions strongly reduced active lever presses during cue-induced drug-seeking. At the neurochemical level, we demonstrated a significant increase in the dopamine D₂-like receptor density in the prefrontal cortex in animals following drug abstinence in isolation cage or enriched environment conditions, and the reduction in their density in the dorsal striatum provoked by isolation cage conditions. The metabotropic glutamate type 5 receptor density decreased only in the prefrontal cortex after isolation cage and enriched environment abstinence.

Conclusions:

This study shows the different impacts caused by the type of housing conditions during abstinence from cocaine self-administration on drug-seeking behaviour in rats. The observed changes in the dopamine D₂-like and metabotropic glutamate type 5 receptor B_max and/or K_d values were brain-region specific and related to either pharmacological and/or motivational features of cocaine.

Keywords

Environmental conditions drug abstinence metabotropic glutamate type 5 receptor cocaine self-administration

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References

Arndt

Johns

Dietz

et al . (2015) Environmental condition alters amphetamine self-administration: Role of the MGluR₅ receptor and schedule of reinforcement. Psychopharmacology (Berl) 232: 3741–3752.

Arnsten

(2009) The emerging neurobiology of attention deficit hyperactivity disorder: The key role of the prefrontal association cortex. J Pediatr 154: I–S43.

Baker

Tran-Nguyen

Fuchs

et al . (2001) Influence of individual differences and chronic fluoxetine treatment on cocaine-seeking behavior in rats. Psychopharmacology (Berl) 155: 18–26.

Bardo

Klebaur

Valone

et al . (2001) Environmental enrichment decreases intravenous self-administration of amphetamine in female and male rats. Psychopharmacology (Berl) 155: 278–284.

Bardo

Robinet

Hammer

Jr (1997) Effect of differential rearing environments on morphine-induced behaviors, opioid receptors and dopamine synthesis. Neuropharmacology 36: 251–259.

Bennett

Wichems

Hollingsworth

et al . (1995) Novel 2-substituted cocaine analogs: Uptake and ligand binding studies at dopamine, serotonin and norepinephrine transport sites in the rat brain. J Pharmacol Exp Ther 272: 1176–1186.

Ben-Shahar

Obara

Ary

et al . (2009) Extended daily access to cocaine results in distinct alterations in Homer 1b/c and NMDA receptor subunit expression within the medial prefrontal cortex. Synapse 63: 598–609.

Berridge

Robinson

(1998) What is the role of dopamine in reward: Hedonic impact, reward learning, or incentive salience? Brain Res Brain Res Rev 28: 309–369.

Brenes

Fornaguera

(2008) Effects of environmental enrichment and social isolation on sucrose consumption and preference: Associations with depressive-like behavior and ventral striatum dopamine. Neurosci Lett 436: 278–282.

10.

Borgkvist

Malmlöf

Feltmann

et al . (2012) Dopamine in the hippocampus is cleared by the norepinephrine transporter. Int J Neuropsychopharmacol 15: 531–540.

11.

Brown

Mustafa

Ayoub

et al . (2012) mGlu5 receptor functional interactions and addiction. Front Pharmacol 3: 84.

12.

Caine

Thomsen

Gabriel

et al . (2007) Lack of self-administration of cocaine in dopamine D1 receptor knockout mice. J Neurosci 27: 13140–13150.

13.

Chauvet

Lardeux

Goldberg

et al . (2009) Environmental enrichment reduces cocaine seeking and reinstatement induced by cues and stress but not by cocaine. Neuropsychopharmacology 34: 2767–2778.

14.

Coleman

Weed

Schapiro

(2013) Environmental enrichment for animals used in research. In: Conn

(ed.) Animal Models for the Study of Human Disease. London: Academic Press, pp.75–94.

15.

Del Arco

Segovia

Canales

et al . (2007a) Environmental enrichment reduces the function of D1 dopamine receptors in the prefrontal cortex of the rat. J Neural Transm 114: 43–48.

16.

Del Arco

Segovia

Garrido

et al . (2007b) Stress, prefrontal cortex and environmental enrichment: Studies on dopamine and acetylcholine release and working memory performance in rats. Behav Brain Res 176: 267–273.

17.

Di Chiara

(2002) Nucleus accumbens shell and core dopamine: Differential role in behavior and addiction. Behav Brain Res 137: 75–114.

18.

Duman

Malberg

Thome

(1999) Neural plasticity to stress and antidepressant treatment Biol Psychiatry 46: 1181–1191.

19.

El Rawas

Thiriet

Lardeux

et al . (2009) Environmental enrichment decreases the rewarding but not the activating effects of heroin. Psychopharmacology (Berl) 203: 561–570.

20.

European Monitoring Centre for Drugs and Drug Addiction (2016) European Drug Report 2016. Available at: www.emcdda.europa.eu/edr2016 (accessed May 2016)

21.

Frankowska

Marcellino

Adamczyk

et al . (2013) Effects of cocaine self-administration and extinction on D2-like and A2A receptor recognition and D2-like/Gi protein coupling in rat striatum. Addict Biol 18: 455–466.

22.

Garrido

De Blas

Ronzoni

et al . (2013) Differential effects of environmental enrichment and isolation housing on the hormonal and neurochemical responses to stress in the prefrontal cortex of the adult rat: Relationship to working and emotional memories. J Neural Transm 120: 829–843.

23.

Gass

Chandler

(2013) The plasticity of extinction: Contribution of the prefrontal cortex in treating addiction through inhibitory learning. Front Psychiatry 4: 46.

24.

Ghitza

Zhai

et al . (2010) Role of BDNF and GDNF in drug reward and relapse: A review. Neurosci Biobehav Rev 35: 157–171.

25.

Gipson

Beckmann

El-Maraghi

et al . (2011) Effect of environmental enrichment on escalation of cocaine self-administration in rats. Psychopharmacology (Berl) 214: 557–566.

26.

Global Drug Survey (2015) The Global Drug Survey 2015 Findings. Available at: www.globaldrugsurvey.com/the-globaldrug-survey-2015-findings/

27.

Goeders

(2003) The impact of stress on addiction. Eur Neuropsychopharmacol 13: 435–441.

28.

Goldstein

Volkow

(2011) Dysfunction of the prefrontal cortex in addiction: Neuroimaging findings and clinical implications. Nat Rev Neurosci 12: 652–669.

29.

Green

Gehrke

Bardo

(2002) Environmental enrichment decreases intravenous amphetamine self-administration in rats: Dose-response functions for fixed- and progressive-ratio schedules. Psychopharmacology (Berl) 162: 373–378.

30.

Grimm

Osincup

Wells

et al . (2008) Environmental enrichment attenuates cue-induced reinstatement of sucrose seeking in rats. Behav Pharmacol 19: 777–785.

31.

Hajheidari

Miladi-Gorji

Bigdeli

(2015) Effects of environmental enrichment during induction of methamphetamine dependence on the behavioral withdrawal symptoms in rats. Neurosci Lett 605: 39–43.

32.

Hammami-Abrand Abadi

Miladi-Gorji

(2017) Effects of environmental enrichment on behavioral and spatial cognitive deficits in morphine-dependent and -withdrawn rats. Can J Physiol Pharmacol 95: 163–169.

33.

Hammami-Abrand Abadi

Miladi-Gorji

Bigdeli

(2016) Effect of environmental enrichment on physical and psychological dependence signs and voluntary morphine consumption in morphine-dependent and morphine-withdrawn rats. Behav Pharmacol 27: 270–278.

34.

Hearing

Schochet

See

et al . (2010) Context-driven cocaine-seeking in abstinent rats increases activity-regulated gene expression in the basolateral amygdala and dorsal hippocampus differentially following short and long periods of abstinence. Neuroscience 170: 570–579.

35.

Hellemans

Nobrega

Olmstead

(2005) Early environmental experience alters baseline and ethanol-induced cognitive impulsivity: Relationship to forebrain 5-HT1A receptor binding. Behav Brain Res 159: 207–220.

36.

Jastrzebska

Frankowska

Filip

et al . (2016) N-acetylcysteine amide (AD4) reduces cocaine-induced reinstatement. Psychopharmacology (Berl) 233: 3437–3448.

37.

Jastrzębska

Frankowska

Suder

et al . (2017) Effects of escitalopram and imipramine on cocaine reinforcement and drug-seeking behaviors in a rat model of depression. Brain Res 673:30–41.

38.

Jessor

(1980) A social-psychological framework for studying drug use NIDA. Res Monogr 30: 102–109.

39.

Jones

Marsden

Robbins

(1990) Increased sensitivity to amphetamine and reward-related stimuli following social isolation in rats: Possible disruption of dopamine-dependent mechanisms of the nucleus accumbens. Psychopharmacology (Berl) 102: 364–372.

40.

Kalivas

Volkow

Seamans

(2005) Unmanageable motivation in addiction: A pathology in prefrontal-accumbens glutamate transmission. Neuron 45: 647–650.

41.

Kempermann

Kuhn

Gage

(1997) More hippocampal neurons in adult mice living in an enriched environment. Nature 386: 493–495.

42.

Kirkpatrick

Marshall

Clarke

et al . (2013) Environmental rearing effects on impulsivity and reward sensitivity. Behav Neurosci 127: 712–724.

43.

Laviola

Hannan

Macri

et al . (2008) Effects of enriched environment on animal models of neurodegenerative diseases and psychiatric disorders. Neurobiol Dis 31: 159–168.

44.

Levy

Lehre

Rolstad

et al . (1993) A monoclonal antibody raised against an [Na(+)+K+]coupled L-glutamate transporter purified from rat brain confirms glial cell localization. FEBS Lett 317: 79–84.

45.

Marinelli

Piazza

(2002) Interaction between glucocorticoid hormones, stress and psychostimulant drugs. Eur J Neurosci 16: 387–394.

46.

Matthews

Robbins

(2003) Early experience as a determinant of adult behavioural responses to reward: The effects of repeated maternal separation in the rat. Neurosci Biobehav Rev 27: 45–55.

47.

McGlinchey

Aston-Jones

(2018) Dorsal hippocampus drives context-induced cocaine seeking via inputs to lateral septum. Neuropsychopharmacology 43: 987–1000.

48.

Mora

Segovia

del Arco

(2007) Aging, plasticity and environmental enrichment: Structural changes and neurotransmitter dynamics in several areas of the brain. Brain Res Rev 55: 78–88.

49.

Nestler

(2005) The neurobiology of cocaine addiction. Sci Pract Perspect 3: 4–10.

50.

Paxinos

Watson

(1998) The Rat Brain in Stereotaxic Coordinates. 4th ed. Cambridge, MA: Academic Press.

51.

Perry

Zbukvic

Kim

et al . (2014) Role of cues and contexts on drug-seeking behavior. Br J Pharmacol 171: 4636–4672.

52.

Perry

Nelson

Carroll

(2008a) Impulsive choice as a predictor of acquisition of IV cocaine self- administration and reinstatement of cocaine-seeking behavior in male and female rats. Exp Clin Psychopharmacol 16: 165–177.

53.

Perry

Stairs

Bardo

(2008b) Impulsive choice and environmental enrichment: Effects of d-amphetamine and methylphenidate. Behav Brain Res 193: 48–54.

54.

Peters

Kalivas

Quirk

(2009) Extinction circuits for fear and addiction overlap in prefrontal cortex. Learn Mem 16: 279–288.

55.

Petrosini

De Bartolo

Foti

et al . (2009) On whether the environmental enrichment may provide cognitive and brain reserves. Brain Res Rev 61: 221–239.

56.

Pomierny-Chamiolo

Miszkiel

Frankowska

et al . (2015) Withdrawal from cocaine self-administration and yoked cocaine delivery dysregulates glutamatergic mGlu5 and NMDA receptors in the rat brain. Neurotox Res 27: 246–258.

57.

Pomierny-Chamiolo

Miszkiel

Frankowska

et al . (2017) Cocaine self-administration, extinction training and drug-induced relapse change metabotropic glutamate mGlu5 receptors expression: Evidence from radioligand binding and immunohistochemistry assays. Brain Res 1655: 66–76.

58.

Pomierny-Chamioło

Rup

Pomierny

et al . (2014) Metabotropic glutamatergic receptors and their ligands in drug addiction. Pharmacol Ther 142: 281–305.

59.

Puhl

Blum

Acosta-Torres

et al . (2012) Environmental enrichment protects against the acquisition of cocaine self-administration in adult male rats, but does not eliminate avoidance of a drug-associated saccharin cue. Behav Pharmacol 23: 43–53.

60.

Rogers

See

(2007) Selective inactivation of the ventral hippocampus attenuates cue-induced and cocaine-primed reinstatement of drug-seeking in rats. Neurobiol Learn Mem 87: 688–692.

61.

Sale

Berardi

Maffei

(2009) Enrich the environment to empower the brain. Trends Neurosci 32: 233–239.

62.

Scofield

Heinsbroek

Gipson

et al . (2016) The nucleus accumbens: Mechanisms of addiction across drug classes reflect the importance of glutamate homeostasis. Pharmacol Rev 68: 816–871.

63.

Segovia

del Arco

Mora

(2009) Environmental enrichment, prefrontal cortex, stress, and aging of the brain. J Neural Transm 116: 1007–1016.

64.

Sinha

(2001) How does stress increase risk of drug abuse and relapse? Psychopharmacology (Berl) 158: 343–359.

65.

Sinha

(2008) Chronic stress, drug use, and vulnerability to addiction. Ann N Y Acad Sci 1141: 105–130.

66.

Smith

Fetsko

et al . (2002) Dopamine D2L receptor knockout mice display deficits in positive and negative reinforcing properties of morphine and in avoidance learning. Neuroscience 113: 755–765.

67.

Solinas

Chauvet

Thiriet

et al . (2008) Reversal of cocaine addiction by environmental enrichment. Proc Natl Acad Sci USA 105: 17145–17150.

68.

Solinas

Thiriet

El Rawas

et al . (2009) Environmental enrichment during early stages of life reduces the behavioral, neurochemical, and molecular effects of cocaine. Neuropsychopharmacology 34: 1102–1111.

69.

Thanos

Malave

Delis

et al . (2016) Knockout of p11 attenuates the acquisition and reinstatement of cocaine conditioned place preference in male but not in female mice. Synapse 70: 293–301.

70.

Thiel

Engelhardt

Hood

et al . (2011) The interactive effects of environmental enrichment and extinction interventions in attenuating cue-elicited cocaine-seeking behavior in rats. Pharmacol Biochem Behav 97: 595–602.

71.

Thiel

Pentkowski

Peartree

et al . (2010) Environmental living conditions introduced during forced abstinence alter cocaine-seeking behavior and Fos protein expression. Neuroscience 171: 1187–1196.

72.

Thiel

Sanabria

Pentkowski

et al . (2009) Anti-craving effects of environmental enrichment. Int J Neuropsychopharmacol 12: 1151–1156.

73.

Torvinen

Kozell

Neve

et al . (2004) Biochemical identification of the dopamine D2 receptor domains interacting with the adenosine A2A receptor. J Mol Neurosci 24: 173–180.

74.

Twining

Bolan

Grigson

(2009) Yoked delivery of cocaine is aversive and protects against the motivation for drug in rats. Behav Neurosci 123: 913–925.

75.

United Nations Office on Drugs and Crime (2012) World Drug Report 2012. Available at: www.unodc.org/unodc/en/data-and-analysis/WDR-2012.html (accessed June 2012).

76.

United Nations Office on Drugs and Crime (2016) World Drug Report 2016. Available at: www.unodc.org/wdr2016 (accessed May 2016).

77.

van der Harst

Baars

Spruijt

(2003) Standard housed rats are more sensitive to rewards than enriched housed rats as reflected by their anticipatory behavior. Behav Brain Res 142: 151–156.

78.

van Praag

Kempermann

Gage

(2000) Neural consequences of environmental enrichment. Nat Rev Neurosci 1: 191–198.

79.

Volkow

Baler

(2014) Addiction science: Uncovering neurobiological complexity. Neuropharmacology 76: 235–249.

80.

Willner

(2005) Chronic mild stress (CMS) revisited: Consistency and behavioural-neurobiological concordance in the effects of CMS. Neuropsychobiology 52: 90–110.

81.

Wise

(2004) Rewards wanted: Molecular mechanisms of motivation. Discov Med 4: 180–186.

82.

Wise

(2009) Ventral tegmental glutamate: A role in stress-, cue-, and cocaine-induced reinstatement of cocaine-seeking. Neuropharmacology 1: 174–176.

83.

Hou

Gao

et al . (2007) Effects of enriched environment on morphine-induced reward in mice. Exp Neurol 204: 714–719.

84.

You

Chen

Wise

(2001) Dopamine and glutamate release in the nucleus accumbens and ventral tegmental area of rat following lateral hypothalamic self-stimulation. Neuroscience 107: 629–639.

85.

Zhou

Kalivas

(2008) N-acetylcysteine reduces extinction responding and induces enduring reductions in cue- and heroin-induced drug-seeking. Biol Psychiatry 63: 338–340.

86.

Zhu

Apparsundaram

Bardo

et al . (2005) Environmental enrichment decreases cell surface expression of the dopamine transporter in rat medial prefrontal cortex. J Neurochem 93: 1434–1443.

87.

Zhu

Green

Bardo

et al . (2004) Environmental enrichment enhances sensitization to GBR 12935-induced activity and decreases dopamine transporter function in the medial prefrontal cortex. Behav Brain Res 148: 107–117.