Abstract
Background
Evidence indicates that oxytocin, an endogenous peptide well known for its role in
social behaviors, childbirth, and lactation, is a promising addiction pharmacotherapy.
We employed a within-session behavioral-economic (BE) procedure in rats to examine
oxytocin as a pharmacotherapy for methamphetamine (meth) addiction. The BE paradigm
was modeled after BE procedures used to assess motivation for drugs in humans with
addiction. The same BE variables assessed across species have been shown to predict
later relapse behavior. Thus, the translational potential of preclinical BE studies
is particularly strong.
Methods
We tested the effects of systemic and microinfused oxytocin on demand for self-administered
intravenous meth and reinstatement of extinguished meth seeking in male and female
rats using a BE paradigm. Correlations between meth demand and meth seeking were assessed.
Results
Female rats showed greater demand (i.e., motivation) for meth compared with male rats.
In both male and female rats, meth demand predicted reinstatement of meth seeking,
and systemic oxytocin decreased demand for meth and attenuated reinstatement to meth
seeking. Oxytocin was most effective at decreasing meth demand and seeking in rats
with the strongest motivation for drug. Finally, these effects of systemic oxytocin
were mediated by actions in the nucleus accumbens.
Conclusions
Oxytocin decreases meth demand and seeking in both sexes, and these effects depend
on oxytocin signaling in the nucleus accumbens. Overall, these data indicate that
development of oxytocin-based therapies may be a promising treatment approach for
meth addiction in humans.
Keywords
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References
- A brief history of oxytocin and its role in modulating psychostimulant effects.J Psychopharmacol. 2013; 27: 231-247
- Oxytocin in learning and addiction: From early discoveries to the present.Pharmacol Biochem Behav. 2014; 119: 3-9
- Breaking the loop: Oxytocin as a potential treatment for drug addiction.Horm Behav. 2012; 61: 331-339
- Dopamine and oxytocin interactions underlying behaviors: Potential contributions to behavioral disorders.CNS Neurosci Ther. 2010; 16: e92-123
- Oxytocin decreases methamphetamine self-administration, methamphetamine hyperactivity, and relapse to methamphetamine-seeking behaviour in rats.Neuropharmacology. 2010; 58: 38-43
- Role of oxytocin in the neuroadaptation to drugs of abuse.Psychoneuroendocrinology. 1994; 19: 85-117
- The neurobiology of pair bonding.Nat Neurosci. 2004; 7: 1048-1054
- Oxytocin reverses amphetamine-induced deficits in social bonding: Evidence for an interaction with nucleus accumbens dopamine.J Neurosci. 2014; 34: 8499-8506
- Nucleus accumbens oxytocin and dopamine interact to regulate pair bond formation in female prairie voles.Neuroscience. 2003; 121: 537-544
- Intranasal oxytocin blocks alcohol withdrawal in human subjects.Alcohol Clin Exp Res. 2013; 37: 484-489
- Effect of oxytocin on craving and stress response in marijuana-dependent individuals: A pilot study.Psychopharmacology (Berl). 2013; 228: 623-631
- Oxytocin and addiction: A review.Psychoneuroendocrinology. 1998; 23: 945-962
- Oxytocin in the nucleus accumbens core reduces reinstatement of methamphetamine-seeking behaviour in rats.Addict Biol. 2016; 21: 316-325
- Oxytocin reduces cocaine seeking and reverses chronic cocaine-induced changes in glutamate receptor function.Int J Neuropsychopharmacol. 2014; 18
- Anxiolytic effects of oxytocin in cue-induced cocaine seeking behavior in rats.Psychopharmacology (Berl). 2014; 231: 4145-4155
- Economic demand predicts addiction-like behavior and therapeutic efficacy of oxytocin in the rat.Proc Natl Acad Sci U S A. 2014; 111: 11822-11827
- The behavioral, anatomical and pharmacological parallels between social attachment, love and addiction.Psychopharmacology (Berl). 2012; 224: 1-26
- The neural basis of addiction: A pathology of motivation and choice.Am J Psychiatry. 2005; 162: 1403-1413
- Review. Neurobiological mechanisms for opponent motivational processes in addiction.Philos Trans R Soc Lond B Biol Sci. 2008; 363: 3113-3123
- Neuroscience of addiction.Neuron. 1998; 21: 467-476
- The reinstatement model of drug relapse: History, methodology and major findings.Psychopharmacology (Berl). 2003; 168: 3-20
- Dopamine in drug abuse and addiction: Results of imaging studies and treatment implications.Arch Neurol. 2007; 64: 1575-1579
- The neurobiology of craving: Implications for the understanding and treatment of addiction.J Abnorm Psychol. 1988; 97: 118-132
- Neural systems of reinforcement for drug addiction: From actions to habits to compulsion.Nat Neurosci. 2005; 8: 1481-1489
- The behavioral economics of drug self-administration: A review and new analytical approach for within-session procedures.Psychopharmacology (Berl). 2013; 226: 113-125
- Economic concepts for the analysis of behavior.J Exp Anal Behav. 1980; 34: 219-238
- Economic demand and essential value.Psychol Rev. 2008; 115: 186-198
- Reliability and validity of a demand curve measure of alcohol reinforcement.Exp Clin Psychopharmacol. 2009; 17: 396-404
- A behavioral economic analysis of polydrug abuse in alcoholics: Asymmetrical substitution of alcohol and cocaine.Drug Alcohol Depend. 2001; 62: 31-39
- Interrelationships among individual differences in alcohol demand, impulsivity, and alcohol misuse.Psychol Addict Behav. 2014; 28: 282-287
- A comparison of economic demand and conditioned-cued reinstatement of methamphetamine-seeking or food-seeking in rats.Behav Pharmacol. 2011; 22: 312-323
- Orexin-1 receptor signaling increases motivation for cocaine-associated cues.Eur J Neurosci. 2015; 41: 1149-1156
- Behavioral economic assessment of price and cocaine consumption following self-administration histories that produce escalation of either final ratios or intake.Neuropsychopharmacology. 2009; 34: 796-804
- A novel IV cocaine self-administration procedure in rats: Differential effects of dopamine, serotonin, and GABA drug pre-treatments on cocaine consumption and maximal price paid.Psychopharmacology (Berl). 2011; 214: 567-577
- Cocaine self-administration in rats: Threshold procedures.Methods Mol Biol. 2012; 829: 303-319
- Increasing oxytocin receptor expression in the nucleus accumbens of pre-pubertal female prairie voles enhances alloparental responsiveness and partner preference formation as adults.Horm Behav. 2011; 60: 498-504
- Variation in oxytocin receptor density in the nucleus accumbens has differential effects on affiliative behaviors in monogamous and polygamous voles.J Neurosci. 2009; 29: 1312-1318
- Social reward requires coordinated activity of nucleus accumbens oxytocin and serotonin.Nature. 2013; 501: 179-184
- Endocannabinoid signaling mediates oxytocin-driven social reward.Proc Natl Acad Sci U S A. 2015; 112: 14084-14089
- The emerging role of nucleus accumbens oxytocin in social cognition.Biol Psychiatry. 2014; 76: 354-355
- Oxytocin directly administered into the nucleus accumbens core or subthalamic nucleus attenuates methamphetamine-induced conditioned place preference.Behav Brain Res. 2012; 228: 185-193
- Guide for the Care and Use of Laboratory Animals. 8th ed. National Academies Press, Washington, D.C.2011
- Sex differences in methamphetamine seeking in rats: Impact of oxytocin.Psychoneuroendocrinology. 2013; 38: 2343-2353
- Sex differences in escalation of methamphetamine self-administration: Cognitive and motivational consequences in rats.Psychopharmacology (Berl). 2012; 223: 371-380
- Fos activation of selective afferents to ventral tegmental area during cue-induced reinstatement of cocaine seeking in rats.J Neurosci. 2012; 32: 13309-13326
- Systemically administered oxytocin decreases methamphetamine activation of the subthalamic nucleus and accumbens core and stimulates oxytocinergic neurons in the hypothalamus.Addict Biol. 2010; 15: 448-463
- Individual differences in orexin-I receptor modulation of motivation for the opioid remifentanil.Addict Biol. 2017; 22: 303-317
- Sex differences in the acquisition of IV methamphetamine self-administration and subsequent maintenance under a progressive ratio schedule in rats.Psychopharmacology (Berl). 2004; 172: 443-449
- Validity of a demand curve measure of nicotine reinforcement with adolescent smokers.Drug Alcohol Depend. 2011; 113: 207-214
- A behavioral economic measure of demand for alcohol predicts brief intervention outcomes.Drug Alcohol Depend. 2007; 89: 227-233
- Effects of varenicline on abstinence and smoking reward following a programmed lapse.Nicotine Tob Res. 2013; 15: 139-148
- Disruption of maternal parenting circuitry by addictive process: Rewiring of reward and stress systems.Front Psychiatry. 2011; 2: 37
- Selective attenuation of cocaine-induced stereotyped behaviour by oxytocin: Putative role of basal forebrain target sites.Neuropeptides. 1991; 19: 51-56
- Indications for a brain uptake of labelled vasopressin and ocytocin and the problem of the blood-brain barrier.Endokrinologie. 1979; 73: 77-81
- Vasopressin and oxytocin content in cerebrospinal fluid and in various brain areas after administration of histamine and pentylenetetrazol.Pharmacol Biochem Behav. 1983; 19: 587-591
- On the blood-brain barrier to peptides: Accumulation of labelled vasopressin, DesGlyNH2-vasopressin and oxytocin by brain regions.Endocrinol Exp. 1985; 19: 29-37
- Intracellular calcium stores regulate activity-dependent neuropeptide release from dendrites.Nature. 2002; 418: 85-89
- Emergent synchronous bursting of oxytocin neuronal network.PLoS Comput Biol. 2008; 4: e1000123
- Love: An emergent property of the mammalian autonomic nervous system.Psychoneuroendocrinology. 1998; 23: 837-861
- The organization of noradrenergic pathways from the brainstem to the paraventricular and supraoptic nuclei in the rat.Brain Res. 1982; 257: 275-325
- How does stress increase risk of drug abuse and relapse?.Psychopharmacology. 2001; 158: 343-359
- The role of stress in addiction relapse.Curr Psychiatry Rep. 2007; 9: 388-395
- Balance of brain oxytocin and vasopressin: Implications for anxiety, depression, and social behaviors.Trends Neurosci. 2012; 35: 649-659
- Salubrious effects of oxytocin on social stress-induced deficits.Horm Behav. 2012; 61: 320-330
- Modafinil attenuates reinstatement of cocaine seeking: Role for cystine-glutamate exchange and metabotropic glutamate receptors.Addict Biol. 2014; 19: 49-60
- Optogenetic inhibition of cocaine seeking in rats.Addict Biol. 2013; 18: 50-53
- The glutamate homeostasis hypothesis of addiction.Nat Rev Neurosci. 2009; 10: 561-572
- Gq-DREADD selectively initiates glial glutamate release and inhibits cue-induced cocaine seeking.Biol Psychiatry. 2015; 78: 441-451
Article info
Publication history
Published online: December 02, 2016
Accepted:
November 18,
2016
Received in revised form:
October 31,
2016
Received:
April 6,
2016
Identification
Copyright
© Society of Biological Psychiatry, 2016.
