Oxytocin Attenuates the Stress-Induced Reinstatement of Alcohol-Seeking in Male Rats: Role of the Central Amygdala

Factors such as stress and anxiety often contribute to alcohol-dependent behavior and can trigger a relapse of alcohol addiction and use. Therefore, it is important to investigate potential pharmacological interventions that may alleviate the influence of stress on addiction-related behaviors. Previous studies have demonstrated that the neuropeptide oxytocin has promising anxiolytic potential in mammals and may offer a pharmacological target to diminish the emotional impact on reinstatement of alcohol-seeking. The purpose of the present study was to investigate the effect of oxytocin on stress-induced alcohol relapse and identify a neural structure mediating this effect through the use of an ethanol self-administration and yohimbine-induced reinstatement paradigm. While yohimbine administration resulted in the reinstatement of ethanol-seeking behavior, the concurrent administration of yohimbine and oxytocin attenuated this effect, suggesting that oxytocin may disrupt stress-induced ethanol-seeking behavior. The central amygdala (CeA) is a structure that drives emotional responses and robustly expresses oxytocin receptors. Intra-CeA oxytocin similarly attenuated the yohimbine-induced reinstatement of ethanol-seeking behavior. These results demonstrate that oxytocin has the potential to attenuate stress-induced relapse into ethanol-seeking behavior, and that this mechanism occurs specifically within the central amygdala.

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Matrix Metalloproteinase-9 and Synaptic Plasticity in the Central Amygdala in Control of Alcohol-Seeking Behavior

Biological Psychiatry ◽

10.1016/j.biopsych.2016.12.026 ◽

2017 ◽

Vol 81 (11) ◽

pp. 907-917 ◽

Cited By ~ 23

Author(s):

Marzena Stefaniuk ◽

Anna Beroun ◽

Tomasz Lebitko ◽

Olga Markina ◽

Szymon Leski ◽

...

Keyword(s):

Synaptic Plasticity ◽

Matrix Metalloproteinase ◽

Matrix Metalloproteinase 9 ◽

Central Amygdala ◽

Seeking Behavior ◽

Metalloproteinase 9 ◽

Alcohol Seeking

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Targeted overexpression of CRH receptor subtype 1 in central amygdala neurons: effect on alcohol-seeking behavior

Psychopharmacology ◽

10.1007/s00213-018-4908-6 ◽

2018 ◽

Vol 235 (6) ◽

pp. 1821-1833 ◽

Cited By ~ 6

Author(s):

L. Broccoli ◽

S. Uhrig ◽

G. von Jonquieres ◽

K. Schönig ◽

D. Bartsch ◽

...

Keyword(s):

Receptor Subtype ◽

Central Amygdala ◽

Seeking Behavior ◽

Alcohol Seeking

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ATTENUATION OF ALCOHOL-SEEKING BEHAVIOR AND ALCOHOL SELF-ADMINISTRATION BY THE MGLU II AGONIST LY379268

Alcoholism Clinical and Experimental Research ◽

10.1097/00000374-200408002-00077 ◽

2004 ◽

Vol 28 (Supplement) ◽

pp. 19A

Author(s):

P B??ckstr??m ◽

P Hyyti??

Keyword(s):

Self Administration ◽

Seeking Behavior ◽

Alcohol Seeking

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Effects of Ethanol Exposure on Subsequent Acquisition and Extinction of Ethanol Self-Administration and Expression of Alcohol-Seeking Behavior in Adult Alcohol-Preferring (P) Rats: II. Adult Exposure

Alcoholism Clinical and Experimental Research ◽

10.1111/j.1530-0277.2002.tb02466.x ◽

2002 ◽

Vol 26 (11) ◽

pp. 1642-1652 ◽

Cited By ~ 60

Author(s):

Zachary A. Rodd-Henricks ◽

Richard L. Bell ◽

Kelly A. Kuc ◽

James M. Murphy ◽

William J. McBride ◽

...

Keyword(s):

Ethanol Exposure ◽

Self Administration ◽

Seeking Behavior ◽

Adult Exposure ◽

Alcohol Seeking

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Evidence for the role of dopamine D3receptors in oral operant alcohol self-administration and reinstatement of alcohol-seeking behavior in mice

Addiction Biology ◽

10.1111/j.1369-1600.2007.00051.x ◽

2007 ◽

Vol 12 (1) ◽

pp. 35-50 ◽

Cited By ~ 54

Author(s):

Christian A. Heidbreder ◽

Michela Andreoli ◽

Cristina Marcon ◽

Daniel M. Hutcheson ◽

Eliot L. Gardner ◽

...

Keyword(s):

Self Administration ◽

Seeking Behavior ◽

Alcohol Seeking

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Alcohol Seeking Under Risk of Punishment Is Associated With Activation of Cortical and Subcortical Brain Regions

Frontiers in Behavioral Neuroscience ◽

10.3389/fnbeh.2021.739681 ◽

2021 ◽

Vol 15 ◽

Author(s):

Allison J. McDonald ◽

Isis Alonso-Lozares ◽

Vasco Rauh ◽

Yvar van Mourik ◽

Dustin Schetters ◽

...

Keyword(s):

Discriminative Stimulus ◽

Discrimination Task ◽

Brain Regions ◽

Male Rats ◽

Negative Consequences ◽

Self Administration ◽

Higher Alcohol ◽

Cortical Regions ◽

Alcohol Seeking ◽

Motivational Conflict

In humans, stimuli associated with alcohol availability can provoke relapse during abstinence. In this study, we investigated the role of discriminative stimuli (DS) in the control of alcohol seeking in two types of behavioral tests. The first test examined the ability of an alcohol-associated DS to promote alcohol seeking (relapse) after punishment-imposed abstinence in the presence of a different DS. Following this, we tested whether the differentially associated DS can promote and suppress alcohol self-administration in a within-session discrimination task. During the within-session discrimination task, we also tested the rate of alcohol self-administration when two DS are presented in a compound. We first trained Long-Evans male rats (n = 24) to self-administer alcohol in the presence of one DS (reward-associated discriminative stimulus, rewDS) and then punished that behavior in the presence of a different DS (punishment-associated discriminative stimulus, punDS). On the test, we found that rats tested with the rewDS showed higher alcohol seeking than rats tested with the punDS. This result shows that a single Cue DS can promote alcohol seeking in a manner comparable to contexts. Subsequently, we trained 16 of these rats in a within-session trial-based discrimination task, comprised of intervening 2-min trials of rewDS, punDS, or conflict with rewDS and punDS in compound and a reduced probability of punishment. We found that alcohol self-administration is bi-directionally regulated by the rewDS and punDS. In conflict trials, alcohol self-administration was at a rate that was intermediate between the rewDS and punDS trials. In a final test, rats were presented with one of the three trial conditions and perfused for Fos immunohistochemistry. We found Fos expression was higher in the rats tested in the conflict condition in three interconnected sub-cortical brain regions. This study demonstrated the important role that alcohol-associated DS plays an important role in promoting relapse to alcohol seeking after punishment-imposed abstinence. We also implemented a within-session discrimination task that allows for the study of alcohol seeking under motivational conflict, which may be relevant for alcohol use despite negative consequences. The results from the Fos data suggest that higher alcohol seeking in approach-avoidance motivational conflict is associated with activation of sub-cortical regions but not cortical regions.

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Do Prenatally Methamphetamine-Exposed Adult Male Rats Display General Predisposition to Drug Abuse in the Conditioned Place Preference Test?

Physiological Research ◽

10.33549/physiolres.932391 ◽

2012 ◽

pp. S129-S138

Author(s):

R. ŠLAMBEROVÁ ◽

M. POMETLOVÁ ◽

B. SCHUTOVÁ ◽

L. HRUBÁ ◽

E. MACÚCHOVÁ ◽

...

Keyword(s):

Drug Abuse ◽

Pregnant Women ◽

Conditioned Place Preference ◽

Adult Male ◽

Place Preference ◽

Male Rats ◽

Self Administration ◽

Adult Rats ◽

Drug Seeking ◽

Seeking Behavior

Drug abuse of pregnant women is a growing problem. The effect of prenatal drug exposure may have devastating effect on development of the offsprings that may be long-term or even permanent. One of the most common drug abused by pregnant women is methamphetamine (MA), which is also the most frequently abused illicit drug in the Czech Republic. Our previous studies demonstrated that prenatal MA exposure alters behavior, cognition, pain and seizures in adult rats in sex-specific manner. Our most recent studies demonstrate that prenatal MA exposure makes adult rats more sensitive to acute injection of the same or related drugs than their controls. The aim of the present study was to examine the effect of prenatal MA exposure on drug-seeking behavior of adult male rats tested in the Conditioned place preference (CPP). Adult male rats were divided to: prenatally MA-exposed (5 mg/kg daily for the entire prenatal period), prenatally saline-exposed (1 ml/kg of physiological saline) and controls (without maternal injections). The following drugs were used in the CPP test in adulthood: MA (5 mg/kg), amphetamine (5 mg/kg), cocaine (5 and 10 mg/kg), morphine (5 mg/kg), MDMA (5 mg/kg) and THC (2 mg/kg). Our data demonstrated that prenatally MA-exposed rats displayed higher amphetamine-seeking behavior than both controls. MA as well as morphine induced drug-seeking behavior of adult male rats, however this effect did not differ based on the prenatal MA exposure. In contrast, prenatal MA exposure induced rather tolerance to cocaine than sensitization after the conditioning in the CPP. MDMA and THC did not induce significant effects. Even though the present data did not fully confirmed our hypotheses, future studies are planned to test the drug-seeking behavior also in self-administration test.

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