Social and neural determinants of aggressive behavior: pharmacotherapeutic targets at serotonin, dopamine and γ-aminobutyric acid systems
Acute isolation-induced fighting in mice produced a striking 'dose-dependent' increase in Km and Vmax for DA uptake in mesocortical nerve endings (synaptosomes) but no significant changes for these uptake constants in nigrostriatal terminals. The selective response of the mesocortical system to fighting is similar to that reported for other affective paradigms and stress. Several controls were carried out simultaneously to sort out neurotransmitter responses due to aggressive behavior from those due to secondary behaviors which accompany fighting. Non-significant or borderline increases in Km and Vmax for mesocortical DA uptake were noted in (i) animals permitted to witness fighting but prevented from participating, (ii) those subjected to the stress of a mock-fighting situation and (iii) animals simply handled by the investigator, but in no case were the control values increased to the magnitude produced by fighting. (iv) Group-housed animals showed no mesocortical response when placed in the arena with isolated mice. They retired to the corners and would not fight. These mild to negative control findings indicate that the marked cortical responses seen in the fighting animals are not due to (i) anticipation of the fight, (ii) physical stress and motor activity, (iii) placing the animals in the combat arena, or (iv) isolation. Significant changes in nigrostriatal DA reactivity were noted only in the isolated animals prevented from fighting where there was a decrease in Km and Vmax for DA uptake.