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.
Chronic stress impairs auditory attention in rats and monoamines regulate neurotransmission in the primary auditory cortex (A1), a brain area that modulates auditory attention. In this context, we hypothesized that norepinephrine (NE) levels in A1 correlate with the auditory attention performance of chronically stressed rats. The first objective of this research was to evaluate whether chronic stress affects monoamines levels in A1. Male Sprague–Dawley rats were subjected to chronic stress (restraint stress) and monoamines levels were measured by high performance liquid chromatographer (HPLC)-electrochemical detection. Chronically stressed rats had lower levels of NE in A1 than did controls, while chronic stress did not affect serotonin (5-HT) and dopamine (DA) levels. The second aim was to determine the effects of reboxetine (a selective inhibitor of NE reuptake) on auditory attention and NE levels in A1. Rats were trained to discriminate between two tones of different frequencies in a two-alternative choice task (2-ACT), a behavioral paradigm to study auditory attention in rats. Trained animals that reached a performance of ≥80% correct trials in the 2-ACT were randomly assigned to control and stress experimental groups. To analyze the effects of chronic stress on the auditory task, trained rats of both groups were subjected to 50 2-ACT trials 1 day before and 1 day after of the chronic stress period. A difference score (DS) was determined by subtracting the number of correct trials after the chronic stress protocol from those before. An unexpected result was that vehicle-treated control rats and vehicle-treated chronically stressed rats had similar performances in the attentional task, suggesting that repeated injections with vehicle were stressful for control animals and deteriorated their auditory attention. In this regard, both auditory attention and NE levels in A1 were higher in chronically stressed rats treated with reboxetine than in vehicle-treated animals. These results indicate that NE has a key role in A1 and attention of stressed rats during tone discrimination.
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