Social Reactivity and D1 Dopamine Receptors: Studies in Mice Selectively Bred for High and Low Levels of Aggression (original) (raw)
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Pharmacology Biochemistry and Behavior, 1995
tersocial reactivity and D, dopamine receptors in high-and low-aggressive mice. PHARMACOL BIOCHEM BEHAV 51(4) 767-773, 1995. -As a result of selective breeding, NC!900 mice exhibit isolation-induced attacks in a social interaction test, whereas NC100 mice do not attack but freeze instead. Administration of the D, receptor agonist dihydrexidine was previously shown to reduce aggression in NC!900 mice and nonagonistic approaches in NC100 mice. This resulted from induction of a marked social reactivity in both selected lines. Because isolation rearing also induces social reactivity, the present experiment was designed to test the hypothesis that D, dopamine receptors mediate isolation-induced social reactivity. Isolation was expected to potentiate the effects of a D, agonist and to increase D, dopamine receptor density. Thus, isolated and groupreared mice were administered dihydrexidine, and their social behavior was compared to vehicle-injected controls. Dihydrexidine induced higher levels of reactivity among isolated than among group-reared animals, especially in NC!900 mice. In independent experiments, increased densities of D, dopamine receptors in the striatum of isolated animals were found, with no change in affinity. These studies suggest an important role for the D, dopamine receptor as a mediator of isolation-induced social reactivity.
Behavioural Brain Research, 2000
Following isolation housing, mice typically exhibit heightened emotional reactivity to mild social stimulation. Aggression, social avoidance and a variety of defensive behaviors that differ in terms of motor activation (e.g. freezing, escape) can be observed depending on strain. Previous studies suggested that D 2 -like dopamine (DA) receptors play an important, albeit strain specific, role in the mediation of particular forms of defensive behavior. D 3 receptors are subtypes of D 2 -like receptors that are highly expressed in limbic areas of the brain and, therefore, they have been hypothesized to mediate emotional behavior. This study examined the effects of the putative D 3 receptor agonists 7-OH-DPAT and PD128907 on social-emotional behavior in isolated C57BL/6J and A/J mice. These effects were compared with those of the selective D 2 receptor agonist PNU91356A. All three DA agonists increased non-locomotor forms of defensive behavior (e.g. freezing, upright defensive posture). These effects were observed at low doses in C57BL/6J and at higher doses in A/J mice. Only the D 3 receptor agonists were effective in increasing locomotor forms of defensive behavior (i.e. escape, jump) at higher doses. These effects were more pronounced in C57BL/6J mice than A/J mice. The increases in stationary and locomotor defensive behavior were accompanied by marked reduction in social investigation in both the strains. Aggressive behavior was also abolished in the aggressive C57BL/6J strain. These results support previous findings and suggest that DA agonists potentiate defensive behavior and/or social fearfulness. They also suggest that D 3 and D 2 DA receptors differentially modulate the expression of social-emotional reactivity and indicate the importance of strain in examining the effects of DA ligands on emotional behavior.
D1 dopamine receptors and the reversal of isolation-induced behaviors in mice
Behavioural Brain Research, 1998
In a previous study, it was demonstrated that the high rates of social reactivity exhibited by isolated male mice in a dyadic encounter were mediated, at least in part, by an increased sensitivity of the D 1 dopamine receptors. The present research was guided by the hypothesis that the behavioral effects of isolation are reversible, and that changes in dopaminergic function support this reversibility. To this end, mice selectively bred for high and low levels of aggression were reared in isolation from weaning (21 days) to puberty (45 days), at which point they were either assigned to groups or left in isolation until day 69. By comparison to the continuous isolation condition, mice that eventually formed groups exhibited significantly less reactivity in a dyadic test conducted on day 69, showed a reduced response to dihydrexidine (DHX), and a decreased density of D 1 dopamine receptors. This experiment provided evidence for the plasticity of the neurobiological system supporting reactive responses, and confirmed the view that its functional organization is open to experientially-induced changes.
Aberrant responses in social interaction of dopamine transporter knockout mice
Behavioural Brain Research, 2004
The dopamine (DA) transporter (DAT) controls the temporal and spatial resolution of dopaminergic neurotransmission. Disruption of the Dat1 gene in mice leads to increased extracellular DA concentrations and reduced expression of D1-and D2-like receptors in striatum. The mutants are hyperactive in the open field and they display deficits in learning and memory. In humans, dopaminergic dysfunction has been associated with a number of different psychiatric disorders and some of these conditions are accompanied by abnormal social responses. To determine whether social responses were also impaired in DAT knockout (KO) mice, behaviors of group-and isolation-housed animals were compared. All group-housed animals readily established hierarchies. However, the social organizations of the mutants were changed over time. Under both group-and isolation-housed conditions, mutants exhibited increased rates of reactivity and aggression following mild social contact. In isolation, exposure to a novel environment exacerbated these abnormal responses. Regardless of housing context, stereotyped and perseverative patterns of social responses were a common feature of the KO repertoire. In fact, many abnormal behaviors were due to the emergence and predominance of these inflexible behaviors. These data suggest that KO mice may serve as a useful animal model for understanding not only how DA dysfunction contributes to social abnormalities, but also how behavioral inflexibility distorts their social responses.
Social interactions in rats: Behavioral and neurochemical alterations in DSP-4-treated rats
Pharmacology Biochemistry and Behavior, 1994
DSP-4, preceded by zimelidine to prevent serotonin depletion, was administered IP to rats behaving in a defensive-submissive manner in a resident-intruder paradigm. Computer-based ethological analysis revealed the decrease of frequency and duration of defensive episodes and marked increase of offensive aggression. This might suggest an increase of aggressiveness and therefore support the notion of an inhibitory role of the noradrenergic system in aggressive behavior independently of the model used. Dramatically changed attitude toward the partner might also result from fear reduction or inadequate responsiveness to environmental factors because DSP-4-treated rats explored more than controls in stressogenic, highly illuminated area. HPLC analysis showed significant reduction of noradrenaline (NA) concentration in amygdala, hypothalamus, hippocampus, and frontal cortex. Simultaneously there occurred a considerable decrease in dopamine (DA) and serotonin (5-HT), and their metabolite levels. This suggests an attenuated activity of the DA and 5-HT systems that we consider as an effect secondary to NA depletion, which reflects the functional interactions between DA, 5-HT, and NA systems. DSP-4 Locus coeruleus Noradrenaline Monoaminergic interactions Ethological analysis Offense Defense Photo-phobic test Rat
NeuroImage, 2014
Dysfunctional interpersonal behavior is thought to underlie a wide spectrum of psychiatric disorders; however, the neurobiological underpinnings of these behavioral disturbances are poorly understood. Previous molecular imaging studies have shown associations between striatal dopamine (DA) D2-receptor binding and interpersonal traits, such as social conformity. The objective of this study was to explore, for the first time, the role of DA D1-receptors (D1-Rs) in human interpersonal behavior. Twenty-three healthy subjects were examined using positron emission tomography and the radioligand [ 11 C] SCH23390, yielding D1-R binding potential values. Striatal D1-R binding was related to personality scales selected to specifically assess one dimension of interpersonal behavior, namely a combination of affiliation and dominance (i.e., the Social Desirability, Verbal Trait Aggression and Physical Trait Aggression scales from Swedish Universities Scales of Personality). An exploratory analysis was also performed for extrastriatal brain regions. D1-R binding potential values in the limbic striatum (r = .52; p = .015), associative striatum (r = .55; p = .009), and sensorimotor striatum (r = .67; p = .001) were positively related to Social Desirability scores. D1-R binding potential in the limbic striatum (r = −.51; p = .019) was negatively associated with Physical Trait Aggression scores. For extrastriatal regions, Social Desirability scores showed positive correlations in the amygdala (r = .60; p = .006) and medial frontal cortex (r = .60; p = .004). This study provides further support for the role of DA function in the expression of disaffiliative and dominant traits. Specifically, D1-R availability may serve as a marker for interpersonal behavior in humans. Associations were demonstrated for the same dimension of interpersonal behavior as for D2-R, but in the opposite direction, suggesting that the two receptor subtypes are involved in the same behavioral processes, but with different functional roles.
Behavioural Brain Research, 2000
In these experiments we evaluated the relationship between behavioral and brain dopamine (DA) responses to social interactions. Subjects were group housed male mice confronted with a non aggressive male or female conspecific following either repeated defeat (defeated) or repeated non aggressive experiences (social). Defeated mice showed more defensive/submissive reactions then mice of the social group regardless of the opponent sex. However, mice defeated by females showed reduced social exploration without significant differences in non social exploration whilst the opposite was true for mice defeated by male opponents. Non aggressive social interactions enhanced dopamine metabolism in the prefrontal cortex (pFC) of DEFEATED mice regardless of opponent sex. However, only mice defeated by females showed enhanced dopamine metabolism and release in the nucleus accumbens septi (NAS) and olfactory tubercle (OT) following interaction with the non aggressive opponent. Finally, correlation between central and behavioral responses evidenced that 3,4-dihydroxiphenilacetic acid levels in the pFC were positively correlated with defensive behaviors and negatively correlated with non social exploration in mice confronted with male opponents but not in those confronted with females. The latter, showed a significant positive correlation between 3-methoxytyramine (3-MT) levels in the OT and defensive responses and significant negative correlation between social investigation and 3-MT levels in the OT and in the NAS. These results indicate a strict relationship between mesocorticolimbic dopamine transmission and behavior responses to social cues. Moreover, they strongly support the view that mesocorticolimbic DA modulates social behavior by affecting perceptive processing.
Psychopharmacology, 2002
Background and rationale: Aggressive outbursts that result in harm and injury present a major problem for the public health and criminal justice systems, but there are no adequate treatment options. Obstacles at the level of social policy, institutional regulation, and scientific strategy in developing animal models continue to impede the development of specific anti-aggressive agents for emergency and long-term treatments. Objective: To be more relevant to the clinical situation, preclinical aggression research has begun to focus on the neurobiological determinants of escalated aggressive behavior that exceeds species-typical patterns. It is the goal of this review to examine novel pharmacological and molecular tools that target the neural mechanisms for different kinds of aggressive behavior more selectively than previously possible and to outline potential pharmacotherapeutic options.
Effects of opiate antagonists on social and aggressive behavior of isolated mice
Pharmacology Biochemistry and Behavior, 1982
Opiate antagonists naloxone (1 and 1.5 mg/kg IP) and naltrexone 12.5 and 5 mg/kg IP) inhibit aggressive responses of DBA/2 isolated mice, while increasing the duration of some social activities such as sniff-body, sniff-nose and following. At the doses employed naloxone and naltrexone did not ",d'fect motor activity and self-grooming of paired mice. These findings are discussed in terms of the endogenous opioids system involvement in arousability, in the response of the organism to stressful events, in the motivational mechanisms which control social behavior and in the functioning of some neurotransmitter systems which are known to play an important role in the control of isolation-induced aggressive behavior.