The effect of 5-HT2a/2c receptor agonist microinjected into central amygdaloid nucleus and median preoptic area on maternal aggressive behavior in rats

Abstract

The effect of 5-HT 2a/2c receptor agonist microinjected into central amygdaloid nucleus and median preoptic area on maternal aggressive behavior in rats Efeito sobre o comportamento materno agressivo de ratos da microinjeção do agonista seletivo de receptores 5-HT 2a/2c no núcleo central da amígdala e na área pré-óptica medial A b s t r a c t Objective: Much evidence supports the hypothesis that 5-hydroxytryptamine (5-HT) activation is related to the inhibition of aggression. We examined potentially pro-and anti-aggressive effects of the 5-HT 2A/2C receptor agonist on specific brain sites. Method: Female Wistar rats on the 7 th day postpartum were microinjected with the selective 5-HT 2A/2C receptor agonist, α-methyl-5-hydroxytryptamine maleate (0.2 to 1.0 μg/0.2 μl) into the central amygdaloid nucleus and median preoptic nucleus. For each brain area studied, the frequency of the behaviors: locomotion, social investigation, lateral threat, attacks (frontal and lateral), and biting the intruder were compared among the various treatments by an Analysis of Variance, followed when appropriate, by Tukey's test. Results: Microinjection of the selective 5-HT 2A/2C receptor agonist, a-methyl-5-hydroxytryptamine maleate into central amygdaloid nucleus increased maternal aggression in the absence of concurrent changes in non-aggressive behavior. By contrast, microinjection of the selective 5-HT 2A/2C receptor agonist at several dilutions into the median preoptic nucleusdid not alter aggressive behavior. Conclusions: The current and earlier data with pro-and anti-aggressive effects of the 5-HT 2a/2c receptor agonist, when microinjected into the median preoptic nucleus relative to the central amygdaloid nucleus, medial septum and periaqueductal grey area in female rats point to functionally separate serotonin receptor populations in the amygdaloid-septal-hypothalamic and periaqueductal gray matter areas controlling aggressive behavior. It is possible that amygdaloid 5-HT 2a/2c receptors may increase aggressive behavior in lactating females as a result of changes in fear.Keywords: Serotonin agonist; Behavior, animal; Rats, Wistar; Maternal behavior; Violence Resumo Objetivo: Resultados de muitos estudos sustentam a hipótese de que a serotonina (5-HT) está relacionada com a inibição do comportamento agressivo. Foram examinados os efeitos potenciais pró e anti-agressivos do agonista de receptores 5-HT 2A/2C em regiões específicas do cérebro. Método: Ratas fêmeas Wistar no sétimo dia pós-parto receberam microinjeções do agonista seletivo de receptores 5-HT 2A/2C , α-methyl-5-hydroxytryptamine maleate (0,2 a 1,0 μg/0,2 μl), no núcleo central da amígdala e núcleo pré-óptico medial. Para cada área estudada, as freqüências dos comportamentos: locomoção, investigação social, postura de ameaça, ataques (frontal e lateral) e ato de morder um intruso, foram comparadas entre os diferentes tratamentos por uma análise da variância, seguida quando apropriado do teste de Tukey. Resultados: Os resultados mostraram que a microinjeção do agoni...

Focus on HTR2C: A possible suggestion for genetic studies of complex disorders

“…These lines of evidence seem to be consistent with the serotonergic theory of anxiety disorder, even though conflicting reports can be found as well [Beckett and Marsden, 1997;Shaikh et al, 1997]. Interestingly, as for the opposite behavioral effects determined after HTR2C stimulation in the VTA and NAs reported before, stimulation of the HTR2C in the PAG is associated with anti-anxiety effect, whilst stimulation of HTR2C in the limbic forebrain (amygdala and hippocampus) has been reported to be associated with anxiety like or aggressive behavior [de Almeida et al, 2006;Cornelio and Nunes-de-Souza, 2007;Nunes-de-Souza et al, 2008]. These lines of evidence may suggest the presence of diverse HTR2C populations, or, better, the expression of HTR2C receptors in the surface of interneurons embedded in inhibitory or facilitative pathways in the midbrain and limbic forebrain respectively.…”

“…The role of the amygdala seems to be specific to the innate fear response since that this anxiety like behavior elicited by HTR2C agonists was undetectable when the ventral or dorsal hippocampus were stimulated [Cornelio and Nunes-de-Souza, 2007]. Consistently, an aggressive behavior was achieved after administration of an HTR2C agonist in the central nucleus of amygdala, in female rats selected at the 7th day after partum [de Almeida et al, 2006]. Maybe not surprisingly, HTR2C agonist effect in the basolateral amygdala-detected as a c-fos activation-is also associated with a diminished appetite in animal models [Somerville et al, 2007].…”

C-Fos identification of neuroanatomical sites associated with haloperidol and clozapine disruption of maternal behavior in the rat

“…Brunner et al (1999) reported that 5-HT 1B receptor knockout mother mice did not display pup retrieval deficits. Other studies found that 5-HT 1B and 5-HT 2A/2C receptors are involved in maternal aggressive behavior (De Almeida et al, 2005, 2006a, 2006b; Olivier et al, 1995; Veiga et al, 2007). Recently, Lerch-Haner et al (2008) reported that transgenic mouse dams with a specific disruption in serotonin transcription factor displayed profound maternal deficits (e.g., pup retrieval, pup nursing, nest building).…”

Monoamine-Sensitive Developmental Periods Impacting Adult Emotional and Cognitive Behaviors

“…Together, these studies demonstrate a broad involvement of 5-HT 1 receptor-type signaling in modulating, mostly inhibiting, aggressive behavior. Local infusion of 5-HT 2A/2C receptor agonist into the corticomedial amygdaloid nucleus increases, but infusion into the dorsal PAG reduces aggression in female rats (de Almeida et al, 2005b(de Almeida et al, , 2006. Interestingly, orbitofrontal availability of 5-HT 2A receptors assessed through PET imaging is higher in personality disorder patients with physical aggression when compared with patients without aggression or healthy controls (Rosell et al, 2010).…”