The Potential Role of Serotonin1A Receptors in Post-weaning Social Isolation–Induced Abnormal Behaviors in Rodents

Abstract

Abstract. Post-weaning social isolation in mice induces behavioral abnormalities such as hyperactivity, aggression, depression-and anxiety-like behaviors, deficits of prepulse inhibition, and reduced pain sensitivity to the noxious stimuli. Then, this mouse is considered to be a model of psychiatric disorders including schizophrenia. We have found that serotonin (5-HT) 1A -receptor ligands attenuate these abnormalities, suggesting the pharmacological role of the receptor in treatment of psychiatric disorders. Furthermore, we have recently found that isolation-reared mice show social encounter-induced hyperactivity, a novel phenotype of the abnormal behaviors, and the hyperactivity is triggered by activation of the serotonergic system from the dorsal raphe to the frontal cortex. This review summarizes the effects of 5-HT 1A receptor ligands on aggressive behavior, deficits of prepulse inhibition, reduced pain sensitivity to the noxious stimuli, and encounter-induced hyperactivity in social isolation-reared mice. These findings suggest that the 5-HT 1A receptor is a potential target molecule for treatment of psychiatric disorders and pain.

Effects of Activation and Blockade of Serotonin 5-HT1A Receptors on the Immune Response in Rats Selected for Different Levels of Aggressiveness

“…Excessive aggression is a symptom in a variety of neuropsychiatric disorders, such as schizophrenia, depression, anxiety disorder, and substance abuse [1]- [4], which have long been known to be associated with immune dysfunctions [5]- [8]. Consistent with clinical observations, data obtained on the basis of several animal models (isolation housing, social interactions or genetic predisposition) have indicated that aggressive behavior is accompanied with altered immune reactivity [9]- [22].…”

“…Moreover, a number of studies indicate that activation of presynaptic 5-HT 1A receptors having the effect of inhibitory regulation on the release of 5-HT, may stimulate the release of DA in several corticolimbic areas [4] [46]. These brain structures are also considered to play a role in immunostimulation [12] [30] [47]- [49].…”

“…Immune abnormalities under aggression may be related to changes in serotonin (5-HT) neurotransmission and functional activity of 5-HT 1A receptors which have been implicated not only in mediating aggressive behaviors [1]- [4] [23]- [25], but also in neuroimmunomodulation both in normal and psychoemotional stress conditions [12] [26]- [31].…”

Role of the 5-HT1A autoreceptor in the enhancement of fluvoxamine-induced increases in prefrontal dopamine release by adrenalectomy/castration in mice

“…These findings suggest that the prefrontal dopaminergic system is regulated by an interaction between 5-HT 1A and s 1 receptors, but the detailed mechanism for this interaction is not known. 5-HT 1A receptors are considered to be a potential target molecule for treatment of psychiatric disorders and pain (5), and they are localized not only in 5-HT-containing neurons as the autoreceptors but also in other neurons as postsynaptic receptors (6). The present study examined which 5-HT 1A autoreceptors or postsynaptic receptors play a key role in the enhancement of fluvoxamine-induced increases in prefrontal dopamine release by adrenalectomy/castration in mice.…”

Role of prefrontal serotonergic and dopaminergic systems in encounter-induced hyperactivity in methamphetamine-sensitized mice

“…Aggressive behavior and impaired social interactions are observed in rodent models of psychiatric disorders such as schizophrenia (Sams-Dodd, 1999; Jones et al, 2011; Ago et al, 2014). The response to an encounter with an intruder, a psychological stress, is an example of these abnormal behaviors, and it often involves aggressive contact (i.e., biting attacks, wrestling, and lateral threats) between 2 rodents.…”