?2 and ?-adrenoceptor agonists modulate [3H]dopamine release from rat nucleus accumbens slices: Implications for research into depression

Abstract

The modulatory effects of noradrenergic agonists on the 25 mM K+-induced release of [3H]dopamine (3H-DA) from rat brain nucleus accumbens slices was investigated, using a superfusion technique. The K+-induced release of 3H-DA was Ca2+ dependent, significantly enhanced (25-32%; p less than 0.02) by the beta-adrenoceptor agonist isoproterenol (10 microM), and significantly decreased (13-25%; p less than 0.05) by the alpha 2-adrenoceptor agonist clonidine (10 microM). At these concentrations neither drug affected basal release of 3H-DA. Clonidine (100 microM) increased the basal release of 3H-DA, while decreasing the K+-induced release by 19% (p less than 0.01). The inclusion of desipramine in the incubation medium, to prevent accumulation of 3H-DA into noradrenergic neurons, did not alter the inhibitory effect of clonidine (10 microM) on 3H-DA release. This study provides direct evidence that noradrenergic neurons can modulate dopaminergic neurotransmission in the mesolimbic system.

On the role of noradrenaline in psychostimulant-induced psychomotor activity and sensitization

“…The failure of these noradrenergic drugs to affect the locomotor effect of the dopamine agonist apomorphine suggests that their effects on amphetamine-induced locomotor hyperactivity are mediated upstream from nucleus accumbens output neurons (Kelly et al 1975), for instance through modulation of the activity of mesoaccumbens dopamine neurons. Indeed, in the nucleus accumbens, stimulation a 2 -receptors decreases, and stimulation of b-receptors enhances dopamine release (Nurse et al 1984;Yavich et al 1997). Also, stimulation of a 1 -receptors in the ventral tegmental area (VTA), the cell body area of the mesocorticolimbic dopamine system, enhances the activity of dopamine cells (Grenhoff and Svensson 1993;Shi et al 2000), through suppression of inhibitory glutamatergic transmission (Paladini et al 2001).…”

“…Interestingly, close interactions between dopamine and noradrenaline neurotransmission have been described in brain areas important for psychostimulant-induced hyperactivity and sensitization, such as the nucleus accumbens, ventral tegmental area and prefrontal cortex (Nurse et al 1984;Grenhoff and Svensson 1993;Yavich et al 1997;Nicola and Malenka 1998;Vanderschuren et al 1999;Shi et al 2000;Paladini et al 2001). It is therefore quite conceivable that some of the behavioral effects of amphetamine and cocaine require changes in noradrenaline neurotransmission.…”

Characterization of the effects of serotonin on the release of [3H]dopamine from rat nucleus accumbens and striatal slices

“…It is possible that disturbances in noradrenergic and/or serotonergic modulation of dopamine (DA) release may underlie this defect. We have previously reported on the modulation of DA release from rat brain nucleus accumbens slices by e~2-and [~-adrenoceptor agonists (3), and the effect of chronic antidepressant treatment on this modulation (4, 5). In the present study the effect of serotonin receptor agonists on the release of 403 from rat brain nucleus accumbens and striatal slices has been investigated using a superfusion technique.…”

Accumbal noradrenaline that contributes to the alpha-adrenoceptor-mediated release of dopamine from reserpine-sensitive storage vesicles in the nucleus accumbens is derived from alpha-methyl-para-tyrosine-sensitive pools

“…Both in vitro and in vivo experiments have revealed that stimulation of postsynaptic alpha-adrenoceptors that are located on dopaminergic neurons inhibits the release of dopamine in the nucleus accumbens, whereas inhibition of these receptors stimulates the release of dopamine in this brain structure (Nurse et al 1984(Nurse et al , 1985Russell et al 1988Russell et al , 1993Tuinstra and Cools 2000a;Cools and Tuinstra 2003; see also . It is generally accepted that presynaptic alpha-adrenoceptors regulate the amount of noradrenaline in the synapse and, accordingly, regulate the amount of noradrenaline at the level of postsynaptic alphaadrenoceptors.…”