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Item does not contain fulltext, The effects of intra-accumbal infusion of selective agonists for the beta-adrenoceptor subtypes on the noradrenaline and dopamine efflux in the nucleus accumbens of freely moving rats were investigated, using in vivo microdialysis. Neither beta1-(dobutamine: 0.06 and 0.12 pmol) nor beta2-adrenoceptor agonist (salbutamol: 0.36 and 3.6 pmol) altered the basal noradrenaline and dopamine efflux in the nucleus accumbens. Co-administration of 0.06 pmol of dobutamine with salbutamol (3.6 pmol) did not affect the noradrenaline levels, but it increased the dopamine efflux to approximately 120%. Co-administration of 0.12 pmol of dobutamine with salbutamol (0.36 or 3.6pmol) also increased DA efflux to approximately 120% without affecting noradrenaline levels. The non-selective beta-adrenoceptor antagonist l-propranolol (1200 pmol) that did not alter the basal noradrenaline and dopamine levels, suppressed the dopamine efflux, induced by co-administration of dobutamine (0.12 pmol) and salbutamol (3.6 pmol). The doses mentioned are the total amount of drug over the 60-min infusion period. The present results support our previously reported conclusion that stimulation of accumbal beta-adrenoceptors which are suggested to be postsynaptically located on accumbal dopaminergic terminals, can enhance the dopamine efflux in the nucleus accumbens. The present study also provides in vivo neurochemical evidence that concomitant, but not separate, activation of accumbal beta1- and beta2-adrenoceptors synergistically increases the accumbal dopamine efflux.

1 februari 2012, Item does not contain fulltext, GABA released from accumbal GABAergic interneurons plays an inhibitory role in the regulation of dopamine efflux through GABA(B) and GABA(A) receptors located on accumbal dopaminergic nerve endings. The cytosolic newly synthesised GABA alters vesicular GABA levels and, accordingly, the amount of GABA released from the neuron. Therefore, we hypothesised that glutamic acid decarboxylase (GAD) which generates GABA in accumbal GABAergic neurons, at least partly determines the GABA receptor subtype-mediated GABAergic tonus. To (in)validate this hypothesis, in vivo microdialysis was used to study the effects of an intra-accumbal infusion of the GAD inhibitor l-allylglycine (allylglycine) on the accumbal dopamine efflux of freely moving rats. The intra-accumbal infusion of allylglycine (50.0, 250.0 and 500.0 nmol) dose-dependently increased the accumbal dopamine levels. The co-administration of tetrodotoxin (720 pmol) suppressed the allylglycine (500.0 nmol)-induced dopamine efflux. The intra-accumbal infusion of GABA(B) receptor agonist baclofen (2.5 and 5.0 nmol) inhibited the allylglycine (500.0 nmol)-induced dopamine efflux. The baclofen's effects were counteracted by GABA(B) receptor antagonist saclofen (10.0 nmol). Neither GABA(A) receptor agonist (muscimol: 25.0 and 250.0 pmol) nor antagonist (bicuculline: 50.0 pmol) altered the allylglycine (250.0 and 500.0 nmol)-induced dopamine efflux. The present study provides in vivo neurochemical evidence that newly synthesised GABA that exerts an inhibitory tonus on the accumbal dopaminergic activity, acts at the level of GABA(B) receptors, but not GABA(A) receptors. The present study also shows that there is an allylglycine-insensitive GABA pool that release GABA exerting an inhibitory control of the accumbal dopaminergic activity, at the level of GABA(A) receptors. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'.

Item does not contain fulltext, In vivo microdialysis was used to analyse the role of the alpha(1)- and alpha(2)-adrenoceptor subtypes in the regulation of noradrenaline and dopamine efflux in the nucleus accumbens of freely moving rats. Intra-accumbal infusion of alpha(1)-adrenoceptor agonist methoxamine (24pmol) failed to alter the noradrenaline efflux, but decreased the dopamine efflux. The intra-accumbal infusion of alpha(1)-adrenoceptor antagonist prazosin (6, 600 and 6000pmol) produced a dose-related increase and decrease of the noradrenaline and dopamine efflux, respectively. An ineffective dose of prazosin (6pmol) counteracted the methoxamine (24pmol)-induced decrease of dopamine efflux. The prazosin (6000pmol)-induced increase of noradrenaline efflux, but not the decrease of dopamine efflux, was suppressed by the co-administration of an ineffective dose of methoxamine (0.024pmol). Neither the alpha(2)-adrenoceptor agonist clonidine (300pmol) and UK 14,304 (300pmol) nor the alpha(2)-adrenoceptor antagonist RX 821002 (0.6, 3, 600 and 6000pmol) significantly affected the accumbal noradrenaline and dopamine efflux. The doses mentioned are the total amount of drug over the 60-min infusion period. The present results show that (1) accumbal alpha(1)-adrenoceptors which are presynaptically located on noradrenergic nerve terminals inhibit the accumbal noradrenaline efflux, increasing thereby the accumbal dopamine efflux, (2) accumbal alpha(1)-adrenoceptors which are postsynaptically located on dopaminergic nerve terminals inhibit the accumbal dopamine efflux, and (3) accumbal alpha(2)-adrenoceptors play no major role in the regulation of accumbal efflux of noradrenaline and dopamine.

Contains fulltext : 79748.pdf (publisher's version ) (Closed access), Like dexamphetamine, SKF38393 induces an increase in striatal dopamine efflux which is insensitive for tetrodotoxin, Ca(2+) independent and prevented by a dopamine transporter inhibitor. The dexamphetamine-induced striatal dopamine efflux originates from both the reserpine-sensitive vesicular dopamine pool and the alpha-methyl-para-tyrosine-sensitive cytosolic dopamine pool. Given the similarities between dexamphetamine and SKF38393, we hypothesized that both types of pool also contribute to the striatally applied SKF38393-induced dopamine efflux. Using in vivo microdialysis technique, we analysed the contribution of these pools to the SKF38393-induced striatal dopamine efflux in freely moving rats. The increase of dopamine efflux induced by 1.5 microg SKF38393 was largely prevented by either reserpine (5mg/kg i.p., given 24h earlier) or alpha-methyl-para-tyrosine (250 mg/kg i.p., given 2h earlier), showing that both the vesicular dopamine pool and the cytosolic dopamine pool contribute to the SKF38393-induced increase in striatal dopamine efflux. The sum of the amounts of dopamine that was sensitive to either reserpine or alpha-methyl-para-tyrosine, was greater than 100%, namely 137.6% of the basal dopamine level and 143.9% of the SKF38393-induced dopamine level, suggesting that striatally applied SKF38393 promotes the redistribution of dopamine from vesicles to the cytosol, and vice versa. The finding that the combined treatment of reserpine and alpha-methyl-para-tyrosine only inhibited the SKF38393-induced striatal dopamine efflux till 86.0% of the control, is ascribed to the notion that SKF38393 can also inhibit the re-uptake of dopamine. The latter conclusion has far-reaching consequences for studies in which the effects of SKF38393 are simply ascribed to its dopamine D1 receptor stimulation capacity.

Contains fulltext : 71133.pdf (publisher's version ) (Closed access), In vivo microdialysis was used to study the effects of the locally applied GABA(A) receptor agonist muscimol and GABA(A) receptor antagonist bicuculline on the basal dopamine efflux as well as on the endomorphin-1- and endomorphin-2-induced dopamine efflux in the nucleus accumbens of freely moving rats. Muscimol (2500 pmol) and bicuculline (5 and 10 nmol) increased basal dopamine efflux. Bicuculline (50 pmol) inhibited the muscimol (2500 pmol)-induced dopamine efflux. Muscimol (250 pmol), but not bicuculline (50 and 500 pmol), enhanced the endomorphin-1 (25 nmol)-induced dopamine efflux. Bicuculline (50 pmol) counteracted the muscimol (250 pmol)-induced increase of the endomorphin-1-elicited dopamine efflux. Neither muscimol (25 and 250 pmol) nor bicuculline (50 and 500 pmol) affected the endomorphin-2 (25 nmol)-induced dopamine efflux. The doses mentioned are the total amount of drug over the infusion period (25 or 50 min) that varied across the drugs. The finding that muscimol and bicuculline increased basal dopamine efflux may imply that these drugs acted at different sites. It is suggested that (1) muscimol acts at GABA(A) receptors on GABA-ergic neurons that exert an inhibitory control of dopaminergic neurons and, accordingly, disinhibits these dopaminergic neurons, and that (2) bicuculline acts directly at GABA(A) receptors on dopaminergic neurons and, accordingly, removes the inhibitory control of these dopaminergic neurons. The finding that an agonist, but not antagonist, of GABA(A) receptors enhanced the endomorphin-1's effects might indicate that endomorphin-1 produced a floor effect at the level of GABA(A) receptors located on presynaptic, dopaminergic terminals. Finally, the present results support our earlier reported notion that endomorphin-1 and endomorphin-2 increase accumbal dopamine efflux by different mechanisms.

Contains fulltext : 70690.pdf (publisher's version ) (Closed access), In vivo microdialysis was used to study the effects of the locally applied selective noradrenaline uptake inhibitor reboxetine on the baseline noradrenaline and dopamine efflux in the nucleus accumbens of freely moving rats. The effects of intra-accumbal infusion of the beta-adrenoceptor antagonist l-propranolol on the reboxetine-elicited noradrenaline and dopamine efflux in the nucleus accumbens were also analysed. The intra-accumbal infusion of reboxetine (1.2 and 12 pmol) significantly increased both the accumbal noradrenaline efflux and the accumbal dopamine efflux. The intra-accumbal infusion of the chosen doses of l-propranolol (300 and 1200 pmol) did not alter the accumbal noradrenaline and dopamine efflux. The l-propranolol treatment did not affect the reboxetine-elicited accumbal noradrenaline efflux, but it significantly inhibited the reboxetine-elicited increase of accumbal dopamine efflux. The doses mentioned are the total amount of drug over the infusion period that varied across the drugs (60 or 120 min). The present study shows that the intra-accumbal infusion of selective noradrenaline uptake inhibitor reboxetine increases noradrenaline as well as dopamine efflux in the nucleus accumbens of freely moving rats. This study also indicates that inhibition of accumbal beta-adrenoceptors prevented the increase of the reboxetine-induced accumbal dopamine efflux. It is suggested that the reboxetine-induced increase of the endogenous accumbal noradrenaline activates among others accumbal beta-adrenoceptors that, in turn, stimulate the accumbal release of dopamine.