Clinical and experimental findings have implicated brain α2-adrenoceptors in the regulation of many physiological functions, including sexual activity and stress-related behavior. However, which subtypes of the three α2-adrenoceptors that have now been cloned (α2A, α2B, and α2C) are involved in these controls have yet to be established. Here, we investigated the contribution of α2A-adrenoceptors of the locus ceruleus, the principal source of brain noradrenaline, to exploratory and sexual behaviors. Using administration of antisense oligodeoxynucleotide to inhibit the receptor expression, we found that reductions in brainstem α2A-adrenoceptor mRNA levels and α2-adrenoceptor densities induced by antisense treatment were not accompanied by any changes in the major characteristics of male sexual activity, such as mount latencies and numbers of mounts. However, in sexual behavior tests, antisense-treated male rats had decreased numbers of rearings and thus have higher percentages of behaviors positively correlated with sexual activity. Besides, antisense-treated animals had decreased anxiety in plus-maze tests. The data demonstrate that inhibition of α2A-adrenoceptor expression in the region of the locus ceruleus has an anxiolytic-like effect and facilitates male's attention to female in sexual behavior test.

Neonatal treatments can disrupt prepulse inhibition (PPI) of startle response later in life. Alpha2A-adrenergic receptors (alpha2A-ARs) regulate the release of brain neurotransmitters that may influence PPI. The authors examined the effects of short-term reduction in the neonatal brainstem alpha2A-ARs on subsequent development of this receptor system and acoustic startle reflex in rats. Administration of antisense oligodeoxynucleotide complementary to the alpha2A-ARs on Days 2-4 of life reduced receptor expression in the brainstem by Day 5. The treatment increased alpha2-AR numbers in the cortex, hippocampus, and amygdala at 40 days of age, and in cortex and hypothalamus at 90 days of age. Transient increases in hippocampal and amygdalar alpha2-ARs were accompanied by attenuation of acoustic startle response and impairment of PPI.

Ischemic brain injuries are accompanied by the long-term changes in gene expression in the hippocampus, the limbic system structure, involved in the regulation of key aspects of the higher nervous activity, such as cognitive functions and emotions. The altered expression of genes and proteins encoded by them may be related to the development of post-ischemic psycho-emotional and cognitive disturbances. Activation of neuroinflammation following stroke in the hippocampus has been suggested to play an essential role in induction of long-lasting consequences. Identification of changes in the gene expression patterns after ischemia and investigation of the dynamics of these changes in the hippocampus are the necessary first steps toward understanding molecular pathways responsible for the development of post-stroke cognitive impairments and mental pathologies.

Pathways by which inflammatory stimuli influence behaviors can involve changes in neuronal plasticity, however, the evidence for this is still insufficient. This study aimed to evaluate the effects of chronic lipopolysaccharide (LPS) injected alone or together with tetracycline antibiotic doxycycline (Dox) on the levels of Iba-1, BDNF, Bcl-xL and MMP-9 in brain regions in relation to stress-induced behaviors in the elevated plus-maze (EPM). LPS injected to adult rats every 2 days for a total of 7 injections reduced body weight gain, increased spleen and adrenal weights, decreased locomotor activity, and increased anxiety-like behavior. These effects were associated with increased expression of Iba-1, a well-known marker for activated microglia, in most brain regions investigated. Co-treatment of LPS with Dox attenuated LPS-induced microglial activation and behavioral changes, supporting their relation to the neuroinflammation. LPS administration also produced pro-apoptotic changes in the brain. In the hypothalamus and striatum, the levels of anti-apoptotic protein Bcl-xL were decreased, whereas in the amygdala, a significant increase in MMP-9 protein levels was observed. The levels of Iba-1 as well as MMP-9 in the amygdala positively correlated with the numbers of defecation. The data suggest that mechanisms of anxiety associated with neuroinflammation may involve the increase in MMP-9 levels in the amygdala.