Effect of Xamoterol administration into the shell nucleus accumbens of rats on anxiety-like behavior and emotional memory.

Abstract

Beta-adrenergic receptors are involved in anxiety disorders and help regulate anxiety-like behaviors. The nucleus accumbens (NAc), an important brain structure for emotional regulation and learning, plays a crucial role in anxiety. However, limited research has addressed the specific contribution of the NAc - particularly its noradrenergic mechanisms - in anxiety. This study aimed to investigate the effects of administering different doses of Xamoterol, a partial β1-adrenergic agonist, directly into the NAc shell, to understand its impact on anxiety-related processes and the retrieval of emotional memory. Forty adult male Wistar rats were bilaterally implanted with cannulas targeting the NAc shell. The rats received intra-accumbal Xamoterol at doses of 0.01, 0.1, or 1 μg/1 μl (saline). Five minutes after drug administration, anxiety-like behavior was tested using the Elevated Plus Maze (EPM). Twenty-four hours later, an EPM retention test was conducted to assess emotional memory retrieval. In addition, an open-field test was used to measure spontaneous locomotor activity. One-way ANOVA results showed that intra-accumbal Xamoterol (0.1 and 1 μg) significantly decreased anxiety-like behavior on the EPM. Conversely, head-dipping behavior (a risk assessment measure) was significantly increased at 0.01 and 0.1 μg doses of Xamoterol, which can be interpreted as an anxiolytic effect. Furthermore, higher doses of Xamoterol (0.1 and 1 μg) led to better emotional memory performance compared to the control group. None of the Xamoterol doses produced any significant change in locomotor activity (open-field test). These results suggest that β1-adrenergic receptors in the NAc shell play a role in mediating anxiolytic behavior and enhancing emotional memory retrieval in adult male rats.