Response to stress of mesocortico-frontal dopaminergic neurones in rats after long-term isolation

Abstract

Recent studies suggest that the mesocortico-frontal dopaminergic neurones which originate in the ventral tegmental area (VTA) have an inhibitory role in locomotor activity^1,2. They are also markedly activated under stress^3–5. This effect was shown in rats and mice subjected to electric foot-shocks by measuring either the rate of decline of dopamine (DA) after α-methylparatyrosine treatment³ or the changes in dihydroxyphenylacetic acid (dopac) levels and the dopac/DA ratio^4–6. In rats, stress-induced activation of the dopaminergic neurones was prevented by benzodiazepines^4,5, and studies in BALB/c mice introduced for 2 min into an open field further established the role of dopaminergic neurones in emotional responses⁷. These observations led us to examine the effects of long-term isolation on the activity of the mesocortico-frontal dopaminergic neurones in rats, some of which were subjected to a stressful situation. Indeed, several groups have reported that long-term isolation in rodents induced behavioural disturbances such as increased motor activity^8,9 and aggression^9,10 and hyper-reactivity to a new environment or stressful stimuli^10,11. As measured by the changes in dopac levels or the dopac/DA ratio, we report here that the activity of the mesocortico-frontal dopaminergic neurones was reduced after isolation. This was not the case for the dopaminergic neurones projecting to the nucleus accumbens or the striatum, the rate of DA utilisation in these structures was even enhanced in isolated rats in which the activity of the mesocortico-frontal dopaminergic neurones was markedly reduced. Finally, we will show that a 3-min electric foot-shock session is more effective in enhancing dopac levels or the dopac/DA ratio in the frontal cortex of isolated than grouped rats.