Chronic subordination stress in male tree shrews: Replacement of testosterone affects behavior and central alpha 2-adrenoceptors

Abstract

Subordination stress induced by social defeat in male animals is known to inhibit gonadal functions and it has been discussed whether the resulting deficit in testosterone might play a role in subordination behavior. One of the major transmitter systems involved in regulation of behavior is the noradrenergic system. To analyze whether a testosterone replacement can alter subordination behavior and whether this might be related to changes in the brain noradrenergic system, we quantified alpha 2-adrenoceptors (alpha 2-ARs) in the central nervous system of male tree shrews. Animals were submitted to chronic subordination stress and received testosterone at the same time. Behavior was monitored during all phases of the experiment: the control period of 10 days, the period of social stress lasting 10 days when subordinates were confronted daily with a dominant male, and, subsequently, the stress and treatment period of 18 days when in parallel to the stress, animals received either injections of testosterone or vehicle. Brain alpha 2-ARs were quantified by in vitro receptor autoradiography using the antagonist ligand 3H-RX821002. Locomotor activity decreased significantly during the stress period and was not re-normalized by testosterone. In contrast, testosterone re-normalized scent marking behavior and autogrooming, parameters that had both been reduced due to the subordination stress. Vehicle injections improved none of these behaviors. In 8 of 10 brain regions that were analyzed, numbers of alpha 2-adrenergic binding sites were increased in stressed animals that received vehicle injections, but a difference between testosterone and vehicle injected animals was only observed in five regions. These brain regions are all known to be involved in emotional behavior (anterior hypothalamus, medial nucleus of the amygdala, cingulate cortex) or autonomic regulation, respectively (solitary tract nucleus, dorsal motor nucleus of vagus). Therefore, our data show that testosterone influences behavior of male subordinates and modulates alpha 2-AR expression in their brains. Androgen-mediated alterations in receptors occur in brain regions that are known to be involved in emotionality, e.g., in the anterior hypothalamus which regulates aggressive behavior. One can therefore conclude that alpha 2-ARs contribute to neuronal functions that are responsible for subordination of stress behavior, and that testosterone-induced receptor changes are related to the partial restoration of normal behavior.