Vasopressin in the lateral septum decreases conditioned place preference to amphetamine and nucleus accumbens dopamine release

Abstract

The lateral septum (LS) is a limbic nucleus interconnected with several brain areas involved in the regulation of mood and reward. Vasopressin (AVP) is a neuropeptide that has been related to the effects of drugs of abuse, but its role in the addictive process is poorly understood. LS expresses a high density of AVP 1A receptors (V 1A). The aim of this work was to examine whether the modulation of LS AVP system affects the behavioral and neurochemical responses to amphetamine (AMPH) in male rats. Our results show that AMPH-induced conditioned place preference (CPP) produces a decrease in LS AVP content. Besides, we demonstrate that the microinjection of AVP in the LS impairs the expression of AMPH-induced CPP and that this effect is mediated by the activation of the V 1A receptor in the LS. AVP microinjection in the LS elicited a decrease in neuronal activity in the nucleus accumbens (NAc) in animals subjected to AMPH conditioning. Finally, AVP microinjection in the LS decreased dopamine (DA) release in the NAc. Overall, our data demonstrate that intra-LS AVP diminishes the expression of AMPH conditioning behavior while decreasing neuronal activity and DA release in the NAc. Presumably, the effects of AVP in the LS produce an inhibition of GABAergic projections to the VTA, increasing local inhibitory tone in this nucleus, which in turn reduces the activity of DA projections to NAc. Thus, these results contribute to the knowledge about the role of AVP in LS in regulating the reward circuit and addictive like behaviors.

Effect of acute alcohol intoxication on scale-free neural activity in the lateral septum in rats

“…The lateral septum (LS) is a part of the limbic and reward system which sends afferent and efferent projections to many subcortical and cortical brain areas including the ventral tegmental area, amygdala, bed nucleus of stria terminalis, nucleus accumbens, hippocampus, prefrontal cortex, etc. It is suggested that LS is involved in the formation of wide class of addictions and for instance AUD (Deng et al, 2019;Gárate-Pérez et al, 2021). In the current model of addiction, cycle the role of LS has not been determined unequivocally, implying that LS participates in formation of associations between alcohol and contextual stimuli, goalmotivated behaviour and its shift to habit that is observed in addiction, regulation of stress response, memory and emotion development.…”

“…In the current model of addiction, cycle the role of LS has not been determined unequivocally, implying that LS participates in formation of associations between alcohol and contextual stimuli, goalmotivated behaviour and its shift to habit that is observed in addiction, regulation of stress response, memory and emotion development. Manipulations with LS changed the course of addiction eliminating the rein-forcing action of alcohol (Jonsson et al, 2017), blocking conditional place preference for different substance of abuse (Sartor & Aston-Jones, 2012;Gárate-Pérez et al, 2021), attenuating intake and preference of alcohol (Ryabinin et al, 2008).…”

Role of Oxytocin and Vasopressin in Neuropsychiatric Disorders: Therapeutic Potential of Agonists and Antagonists

“…Supporting these findings, a decrease of AVP content has been observed in the hypothalamus after 4 days of cocaine treatment, suggesting that the increase in AVP release at the hypothalamic level is followed by a depletion of this neuropeptide content in this region [ 82 ]. Recent studies from our laboratory showed that amphetamine (AMPH) induced conditioned place preference (CPP) and produced a decrease in AVP content in the LS nucleus, which is interconnected with areas linked to the regulation of mood and reward [ 83 , 84 ]. Moreover, the chronic administration of opiates (e.g., morphine) has been shown to differentially alter OT expression in various brain areas, including a decrease of OT in SON and NAc, and an increase in VTA [ 85 ].…”

“…Indeed, AVP-deficient animals did not develop cocaine sensitization, suggesting that AVP could participate in the addiction process [ 101 ]. Contrary to this evidence, our group recently demonstrated that the microinjection of AVP in LS impairs the expression of AMPH-induced CPP and that this effect is mediated by the activation of the V 1A R in the LS, which could produce the inhibition of GABAergic projections to the VTA, increasing the inhibitory tone in this nucleus, and therefore inducing a decrease in the dopaminergic activity at the NAc [ 84 ]. Moreover, animal studies suggest that the blockade of V 1B R (but not V 1A R) decreases the high level of intake in dependent animals and diminishes the emotional response to a stressor during withdrawal for cocaine [ 86 ].…”

Histochemical characteristics of nitrergic neuronal system during acute alcohol intoxication and nNOS blockage in the rat lateral septum

“…LS має зв'язки з усіма ключовими структурами, задіяними в формуванні залежності. За останні роки з'явилася низка робіт, які доводять участь септальної ділянки у розвитку залежності, особливо в контексті встановлення асоціативних зв'язків між алкоголем і тригерними стимулами [6,8,12,15,28,33].…”