Social Reactivity and D1 Dopamine Receptors: Studies in Mice Selectively Bred for High and Low Levels of Aggression

Abstract

Robust individual differences in social behavior have been ob tained by selectively breeding Institute for Cancer Research mice for high and low levels of aggression. As previously shown, when paired with a non-selected, group-housed partner mouse, NC900 mice exhibit isolation-induced aggression. Conversely, NClDO mice fail to attack, freezing upon social contact. Previous studies have established that NClDO mice have lower dopamine concentrations in nucleus accumbens and caudate nucleus, with increased dopamine receptor densities in these same regions. Thus, we wished to determine the effect of administration of a dopamine receptor agonist on social behavior. Mice of both lines were administered 0, 1, 3, or lD mglkg (SC) of the full efficacy Dl receptor agonist dihydrexidine, and their behavior was assessed in a social interaction test. Dihydrexidine reduced aggression in NC900 mice and nonagonistic approach in NelDO mice in a dose dependent manner. In both cases, this resulted from induction of a marked reactivity to mild social stimulation as measured by increases in behaviors such as escape, reflexive kicking, and vocalizations. Dihydrexidine had no systematic effect on the freezing behavior characteristic of the low-aggressive line. In independent experiments, mice were pretreated with either the Dl antagonist SCH-23390 (.1 mglkg) or the selective D2 antagonist remoxipride (1.0 mglkg), after which they received dihydrexidine (lD mgl kg) and were tested as above. The effects of dihydrexidine on social reactivity in mice of both lines were significantly antagonized by SCH-23390 but not attenuated by remoxipride. Antagonist pretreatment neither reinstated attack in the NC900 line nor non agonistic approach behavior in the NClDO line, which suggests the importance of DI1D2 interactions to the initiation of action. These studies suggest an important role for Dl dopamine receptors in the emotional response to social stimuli. [Neuropsychopharmacology 10:115-122, 1994J genetic background, but differ reliably in the expres sion of a speciflc behavioral trait. High or low levels of open-fIeld activity, alcohol preference, "emotionality, " and aggression are just some of the numerous be havioral characteristics that have been selectively bred with success (Fuller and Thompson 1978). The control of genetic background through selective breeding offers a useful technique for examining the neurobiological mechanisms that mediate the expression of speciflc be havioral traits. The same procedure also allows for ex amination of how the central nervous system mediates the interaction of experience with genetic background in the expression of individual differences.We have been involved in a selective breeding ex periment that is now in its twenty-fIfth generation. This

Social and neural determinants of aggressive behavior: pharmacotherapeutic targets at serotonin, dopamine and ?-aminobutyric acid systems

“…However, one perplexing aspect of this research is that both agonists and antagonists at the same receptor subtype decrease aggressive behavior. For example, the D1 agonists dihydrexidine and SKF 38393 reduce aggressive behavior in mice (Tidey and Miczek 1992a;Lewis et al 1994). However, the D1 antagonist SCH 23390 also reduces aggressive behavior (Rodriguez-Arias et al 1998).…”

Aggressive Behavior, Increased Accumbal Dopamine, and Decreased Cortical Serotonin in Rats

“…Therefore, at present, it remains unclear whether there might have been a correlation between the number of aggressive acts or the duration of aggressive behavior and the magnitude of change in accumbal DA or 5-HT levels. Future studies could address this issue more directly by studying selectively bred rat or mouse lines that show high versus low levels of aggressive behavior (Lewis et al, 1994).…”

Child Behavior Problems Increased by Maternal Smoking During Pregnancy

“…The effects are typically associated with rat hyperactive behavior. '* Furthermore, Lewis et al 16 reported that mice, bred selectively for low aggression, had lower DNA concentrations in the NAcc and caudate nucleus than in mice from a highly aggressive strain.…”