Mesolimbic noradrenaline: specificity, stability and dose-dependency of individual-specific responses to mesolimbic injections of alpha-noradrenergic agonists.

The ability of intra-accumbens phenylephrine (PE) and oxymetazoline to potentiate the 'explosive motor behaviour' (EMB) elicited from the deeper layers of the superior colliculus by picrotoxin injections was examined in Wistar rats. Using a dose of intracollicular picrotoxin that was 10 ng lower than the threshold dose for generating EMB, evidence was obtained for the selective potentiation of EMB by alpha-noradrenergic agonists. The PE-induced potentiation was prevented by phentolamine given 48 h prior to PE. Damage caused by multiple injections of intra-accumbens PE prevented the PE-induced effect. It is concluded that the PE-induced effect is accumbens- and noradrenaline-specific. When rats were injected with intervals of 48 h or more, two types of rats could be discerned: responders, i.e. rats that consistently displayed EMB during all trials, and non-responders, i.e. rats that never displayed EMB. When the intertrial interval was 24 h, responders became temporary non-responders, and vice versa. This temporary change in sensitivity was found to be a drug-induced after-effect. The dose-dependency of the PE-induced after-effect in responders differed significantly from that in non-responders. It is concluded that rats belonging to the same strain are nevertheless marked by an individual-specific, neurochemical state within the nucleus accumbens. It is tentatively suggested that responders are marked by noradrenergic neurones with a low firing rate in contrast to non-responders which are marked by noradrenergic neurones with a high firing rate. Finally, evidence was obtained that ergometrine and (3,4-dihydroxyphenylamino)-2-imidazoline (DPI) act simultaneously at dopaminergic sites which are involved in the control of locomotor activity in a familiar environment and at alpha-noradrenergic sites which are involved in the control of EMB elicited from the superior colliculus.