Sex Differences in Noradrenergic Modulation of Attention and Impulsivity in Rats

Rationale: Noradrenaline (NE) is closely related to attentive performance and impulsive control. However, the potential sex differences regarding attention and impulsivity under the noradrenergic modulation have been largely neglected. Therefore, our study aimed to investigate whether male and female rats exhibit differential responses to NE-related drugs during the five-choice serial reaction time task (5CSRT).

Methods: Male and female rats were trained in 5CSRT and administered with different NE drugs after obtaining stable baseline performance: atipamezole, a highly selective α2 receptor antagonist; prazosin, an α1 receptor antagonist; and atomoxetine, a selective NE reuptake inhibitor. Later, prazosin was selected to co-administration with atomoxetine.

Results: Male and female rats exhibited equal learning speed, and no significant baseline differences were found as measured by the 5CSRT. Atomoxetine decreased premature responses in both sexes, but the extent of this reduction was different, with the reduction greater in males. Besides, atomoxetine (1.8 mg/kg) increased the error of omissions in females. The high dose of prazosin (0.5 mg/kg) decreased the accuracy only in male rats, but this was ameliorated by the co-administration with atomoxetine.

Conclusions: Atomoxetine showed significant improvement in impulsivity, but atomoxetine had less beneficial effects on impulsive control in females than in males, and it even impaired attentional performance in female rats. The α1 receptors were mainly responsible for NE drug-related sex differences in attention rather than impulsivity. The results obtained in this study indicate that the sex differences exist in both attention and impulsivity by the modulation of noradrenaline and raise the concern to improve sex-specific treatments.