Peripheral oxytocin treatment modulates central dopamine transmission in the mouse limbic structures

doi:10.1016/0197-0186(86)90138-5

Neurochemistry International

Volume 9, Issue 4, 1986, Pages 481-485

https://doi.org/10.1016/0197-0186(86)90138-5 Get rights and content

Abstract

The effects of subcutaneous (s.c.) oxytocin treatment have been investigated on various parameters of dopaminergic neurotransmission in basal forebrain structures (nucleus olfactorius posterior + nucleus accumbens + septum) of the mouse. Acute oxytocin treatment failed to influence dopamine utilization in the basal forebrain. Following chronic injections of oxytocin (0.2 mg/kg) for 8 8 days, the neuropeptide decreased dopamine utilization. Neither in vivo nor in vitro oxytocin treatment was capable of influencing the in vitro uptake of [³H]dopamine in basal forebrain slices. The spontaneous release of [³H]dopamine (in the presence of 4.2 mM K⁺) from basal forebrain tissue slices was not affected by in vitro or acute or chronic in vivo oxytocin treatment. The stimulated release of [³H]dopamine (in the presence of 30 mM K⁺) was significantly inhibited by chronic in vivo oxytocin administration. Chronic oxytocin treatment decreased the B_max value of [³H]spiroperidol binding in the basal forebrain. The dissociation constant (K_d) of [³H]spiroperidol binding was not influenced by oxytocin. The data indicate that peripheral oxytocin treatment is capable of modifying dopaminergic neurotransmission in mouse basal forebrain regions.

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Cited by (25)

Reversal of oxycodone conditioned place preference by oxytocin: Promoting global DNA methylation in the hippocampus
2019, Neuropharmacology
Citation Excerpt :
These paradoxical effects of OT might be related to the direct actions of OT stimulation on the dopaminergic system. Kovács et al. (1990) showed that both peripheral and central administration of OT acutely increased dopamine utilization within the Acb, while chronic systemin administration of OT decreased dopamine utilization with the basal forebrain of mice (Kovács et al., 1986). However, the choice of OT paradigm and dose seems to be critical in determining the beneficial effects of the drug.
Repeated exposure to the opioid agonist, oxycodone, can lead to addiction. Accumulating evidence has shown that oxytocin (OT), a neurohypophyseal neuropeptide, could reduce the abuse potential of drugs. Recent studies suggest that epigenetic regulation through DNA methylation are involved in neuroadaptations. The current study was conducted to investigate the effects of OT on oxycodone conditioned place preference (CPP) and the epigenetic mechanism of OT in the hippocampus. For induction of CPP, oxycodone (3.0 mg/kg, i. p.) was administrated to male Sprague-Dawley rats once every other day during an eight-day conditioning phase. Global 5-methylcytosine (5-mC) level was determined based on CPP procedure, including acquisition, expression, extinction and reinstatement. We also measured mRNA levels of DNA methyltransferases (Dnmts), ten-eleven translocations (Tets) and synaptic genes (Psd95, Shank2, Gap43, etc.), and determined synaptic density after restraint stress-induced reinstatement of oxycodone CPP. The results showed that OT (2.5 μg, i. c.v.) pretreatment specifically inhibited the CPP acquisition and expression, facilitated the CPP extinction, and abolished restraint stress-induced reinstatement of oxycodone CPP. OT markedly inhibited global 5-mC changes induced by oxycodone CPP in the four phases. Following restraint stress-induced reinstatement of oxycodone CPP, OT significantly increased mRNA levels of Dnmt1, decreased Tet1 mRNA, synaptic proteins and synaptic density in the hippocampus. Our study indicated that reversal of global DNA hypomethylation through OT could significantly attenuate the rewarding effects induced by oxycodone. Our results suggested that OT could be specific manipulation on oxycodone addiction.
Oxytocin prevents the increase of cocaine-related responses produced by social defeat
2019, Neuropharmacology
Citation Excerpt :
It has been hypothesized that there is an association between the oxytocinergic and dopaminergic systems by which they regulate motivational behaviors (Zanos et al., 2014). Central or peripheral administration of OXT acutely increases DA utilization within the NAc, while chronic administration of OXT decreases DA utilization within the basal forebrain of mice (Kovàcs et al., 1986, 1990). In addition, there is strong evidence that OXT plays a role in the rewarding effects of drugs of abuse.
The neuropeptide oxytocin (OXT) plays a critical role in the regulation of social and emotional behaviors. OXT plays a role in stress response and in drug reward, but to date no studies have evaluated its implication in the long-lasting increase of the motivational effects of cocaine induced by repeated social defeat (RSD). During the social defeat procedure, 1 mg/kg of OXT was administered 30 min before each episode of RSD. Three weeks after the last defeat, the effects of cocaine on the conditioned place preference (CPP), locomotor sensitization and the self-administration (SA) paradigms were evaluated. The influence of OXT on the levels of BDNF in the prefrontal cortex (PFC), striatum and hippocampus was also measured. Our results confirm that raising the levels of OXT during social defeat stress can block the long-lasting effects of this type of stress. OXT counteracts the anxiety induced by social defeat and modifies BDNF levels in all the structures we have studied. Moreover, OXT prevents RSD-induced increases in the motivational effects of cocaine. Administration of OXT before each social defeat blocked the social defeat-induced increment in the conditioned rewarding effects of cocaine in the CPP, favored the extinction of cocaine-associated memories in both the CPP and SA, and decreased reinstatement of cocaine-seeking behavior in the SA. In conclusion, the long-lasting effects of RSD are counteracted by administering OXT prior to stress, and changes in BDNF expression may underlie these protective effects.
Opioid addiction: Who are your real friends?
2017, Neuroscience and Biobehavioral Reviews
Citation Excerpt :
These results are reviewed thoroughly by McGregor and Bowen (2012) and Kovács et al. (1998). It has been demonstrated since at least the mid-1980s that increasing oxytocin in the brain dampens heroin reward and decreases self-administration (Kovacs et al., 1985a; Kovacs et al., 1986). Conversely, morphine exposure alters brain levels of oxytocin (Kovacs et al., 1985b; You et al., 2000), indicating a bidirectional interaction between these systems.
Opioid addiction is a chronic and relapsing mental health disorder. However, only some individuals exposed to opioids, either recreationally or during the course of pain management, will develop addiction. The reasons why some individuals develop addiction and some are spared are not fully understood. Studies indicate that it is likely a combination of genetic predispositions and environmental conditions. Given the role of environmental factors in human addiction, this review examines the role of social environments and social interactions in the development of opioid addictive-like behaviors in rodent studies. To date, three major behavioral approaches have been used in these studies, namely social isolation, environmental enrichment, and social housing with a variety of cage-mates that differ in their drug administration conditions. This review highlights the importance of an individual’s social network in influencing the outcomes of drug abuse and the need to further elucidate the molecular mechanisms underlying these effects. Better understanding is likely to contribute to the development of novel and more effective treatments for addiction disorders.
Neuropeptides as neuroprotective agents: Oxytocin a forefront developmental player in the mammalian brain
2014, Progress in Neurobiology
Citation Excerpt :
Licking and grooming upregulates estrogen synthesis in the brain through a pathway to be studied (Caba et al., 2003; Westberry et al., 2010). Several lines of evidence point toward the involvement of gastrointestinal and cardiovascular hormone peptides such as: CCK, gastrin, VIP and OT (Gainer et al., 2002; Jankowski et al., 2004; Morton et al., 2006; Vickers et al., 2008; Welch et al., 2009), NGF, BDNF, and cytokines (Raison et al., 2006; Sofroniew et al., 2001) in neonatal offsprings, acting through vagal, sciatic and perineal sensory afferents (Feng et al., 2009; Huang and Reichardt, 2001; Gutkowska and Jankowski, 2012; Lenz and Sengelaub, 2009; Uvnäs-Moberg and Petersson, 2005) that activate caudal brain stem noradrenergic (Onaka et al., 1995) and mesolimbic dopaminergic activity (Liu and Wang, 2003; Kovacs et al., 1986; Stern and Keer, 1999), inducing steroidogenesis synthesis by neuronal and testicular cells in the neonatal rat (Agis-Balboa et al., 2006; Gerendai and Csernus, 1995). This sensorial stimulation induces the expression of many different proteins throughout the brain which are known to regulate and mediate neuronal plasticity (Chatterjee et al., 2007; Gao and Horvath, 2007; Huang and Reichardt, 2001; Kennedy and Ehlers, 2006).
Oxytocin (OT) plays a major role in the establishment of social bonds. Social bonds are linked to the activation of cell signaling pathways that promote neurotrophic and synaptic maturation, plasticity and memory changes. Anti-social behavior is often associated with abnormalities of cell signaling pathways and/or defective function of brain neurotransmitters within behavioral CNS circuits due to unproper environmental and social factors, such as, diet, stress, chemical, air pollution, and noise, during gestational period or/and during early postnatal development.
OT exerts an important regulatory functions in maternity and parental behaviors, lactation, attachment, bonding, trust, and sensorial functions such as: homeostatic cardiovascular control, satiety, touch, pain, analgesia and sexual behavior. Noteworthy, OT displays important neuroprotective properties against fetal programmed hypertension when administered during early postnatal life, added to its known anabolic properties shown in adult rats, e.g. body weight control, reduces blood pressure, and increases analgesia. This review focuses on the new evidences supporting OT's role as a major neuroprotective nonapeptide provided by its quality to reverse hypertension programmed in utero by undernutrition.
Oxytocin and object preferences in the male prairie vole
2014, Peptides
Citation Excerpt :
Because OT was administered peripherally, it is not possible to conclude that the apparent behavioral differences between OT and the control treatment (SAL) are direct actions on the brain. There is increasing evidence under other conditions that peripherally-administered OT can have behavioral consequences in human and non-human animals [23,25,27]. However, OT only weakly crosses the blood brain barrier (BBB).
The neuropeptide oxytocin has been previously associated with social attachment behaviors in various species. Studies in socially monogamous prairie voles (Microtus ochrogaster) and other species have implicated oxytocin in partner preferences and other social behaviors. In the present study male prairie voles were injected intraperitoneally with either oxytocin or the selective oxytocin antagonist, L-368,899, and were assessed for object preference (for small inanimate toys) 30-min after injection. Object preferences were assessed in animals tested alone or in the presence of their sibling cage mate. Saline-treated controls displayed preferences for the novel object, both when tested alone and in pairs, while oxytocin-treated voles did not demonstrate an object preference, regardless of whether tested alone or in pairs. Finally, oxytocin antagonist treated voles showed preference for the novel object, but only when tested in pairs. These data support a possible involvement of oxytocin and oxytocin receptors in object preference.
Gestational ethanol and nicotine exposure: Effects on maternal behavior, oxytocin, and offspring ethanol intake in the rat
2008, Neurotoxicology and Teratology
Citation Excerpt :
Oxytocin pretreatment can attenuate dopamine utilization in the nucleus accumbens in response to cocaine [6]. Chronic oxytocin injections are also able to inhibit the stimulated release of dopamine in the basal forebrain [33]. It is possible that oxytocin receptor activation may be interfering with D2 receptors in the VTA, potentially leading to fewer incidences of burst firing within VTA projections to the nucleus accumbens, which have been shown to play an important role in the development of addiction [55].
Alcohol consumption and smoking during pregnancy is common, despite the known adverse effects of these drugs on fetal development. Though studies on the effects of each drug separately are published, little is known about the effect of concurrent use of alcohol and nicotine in humans or in preclinical models. In this report, we examined the impact of continuous gestational exposure to both ethanol via liquid diet and nicotine via an osmotic minipump on maternal behavior, offspring ethanol intake, and oxytocin levels in a rat model. Dams were tested for the onset of maternal behavior with litters of unexposed surrogate pups and then killed to examine oxytocin levels within specific brain regions. Drug-exposed offspring reared by surrogate dams were tested for ethanol intake at either adolescence or adulthood, and oxytocin levels were measured in relevant brain regions after behavioral tests. Dams exhibited minor deficits in maternal care, which were associated with lower oxytocin levels in both the ventral tegmental and medial preoptic areas compared to control dams. Prenatal exposure altered sex-specific ethanol intake, with differential effects at adolescence and adulthood. Oxytocin system changes were also apparent in the ventral tegmental and medial preoptic regions of drug-exposed adolescent and adult offspring. These results suggest that dam treatment with ethanol and nicotine can somewhat negatively affect the early rearing environment, and that prenatal exposure to both of these drugs results in drinking behavior differing from what would be expected from either drug alone. Oxytocin's possible involvement in the mediation of these effects is highlighted.

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Peripheral oxytocin treatment modulates central dopamine transmission in the mouse limbic structures

Abstract

Pharmac. Ther.

Eur. J. Pharmac.

Eur. J. Pharmac.

Eur. J. Pharmac.

Life Sci.

Neuropharmacology

Behav. Brain Res.

Eur. J. Pharmac.

Pharmac. Ther.