Rat Nucleus Accumbens Slices Research Articles

Effect of chronic antidepressant treatment on noradrenergic modulation of [ 3H]dopamine release from rat nucleus accumbens and striatal slices

Unlike desipramine, a potent blocker of noradrenaline uptake, the antidepressant drugs, mianserin and citalopram did not, after chronic administration (28 days), attenuate the clonidine-induced inhibition of [3H]dopamine (DA) release from rat nucleus accumbens slices. Mianserin, like desipramine, failed to alter the isoproterenol-induced enhancement of [3H]DA release from rat nucleus accumbens and striatal slices. These findings suggest that antidepressant action does not necessarily involve desensitization of central alpha 2- or beta-adrenoceptors which influence neuronal transmission.

B-HT 920 and B-HT 958: presynaptic effects on electrically evoked 3H-dopamine release from slices of rat nucleus accumbens.

The effects of two thiazoloazepine derivatives, B-HT 920 (6-allyl-2-amino-5,6,7,8-tetrahydro-4H-thiazolo[4,5-d]azepine) and B-HT 958 (2-amino-6-(p-chloro-benzyl)-4H-5,6,7,8-tetrahydrothiazolo[5,4-d]a zepine) on electrically evoked overflow of 3H-dopamine were studied. Slices from nucleus accumbens of the rat were preincubated with 3H-dopamine and superfused at 23 degrees C or 37 degrees C. Electrical field stimulation was applied using frequencies of 0.5 or 5 Hz. At 37 degrees C/5 Hz, B-HT 920 markedly and dose-dependently (0.01-0.1 mumol/l) reduced the stimulation evoked overflow of tritium. Its dose-response curve was shifted to the right at 23 degrees C/0.5 Hz and 23 degrees C/5 Hz, respectively. A similar result was obtained with the dopamine receptor agonist, apomorphine (1 mumol/l). B-HT 958 (0.1-10 mumol/l) also reduced electrically induced overflow of tritium at 37 degrees C/5 Hz, had no effect at 23 degrees C/0.5 Hz, and facilitated tritium overflow at 23 degrees C/5 Hz. Sulpiride (10 mumol/l) completely prevented the effects of B-HT 920 (1 mumol/l) or B-HT 958 (1 mumol/l) at 37 degrees C/5 Hz, whereas phentolamine (1 mumol/l) had no effect on the actions of the two drugs under these experimental conditions. From the patterns of effects obtained under the different experimental conditions it is concluded that B-HT 920 acts as full agonist at presynaptic dopamine autoreceptors whereas B-HT 958 acts as partial agonist.

Muscarinic receptors discriminated by pirenzepine are involved in the regulation of neurotransmitter release in rat nucleus accumbens.

The effect of pirenzepine, a selective muscarinic antagonist, was tested on the oxotremorine facilitation of the K+-evoked release of [14C]-dopamine from tissue slices of rat nucleus accumbens. The effect of pirenzepine was compared with that of scopolamine and other antagonists which show no heterogeneity in their action on muscarinic receptors in order to determine whether a selective action at a single receptor subtype, M1 or M2, could be distinguished. Pirenzepine and scopolamine both antagonized the oxotremorine-induced (EC50 = 3 X 10(-7) M) facilitation of [14C]-dopamine release with pA2 values of 7.5 and 8.9 respectively. This result indicated that the high affinity pirenzepine receptor (M1) was involved in this response. Low concentrations of 3-quinuclidinyl benzilate (3 X 10(-10) M), N-methylscopolamine (3 X 10(-9) M) and methyl atropine (10(-8) M) also abolished this facilitatory effect of oxotremorine.

Effect of chronic desipramine treatment on adrenoceptor modulation of [ 3H]dopamine release from rat nucleus accumbens slices

The effects of α 2- and β-adrenoceptor agonists on the 25 mM K +-induced release of [ 3H]dopamine ([ 3H]DA from nucleus accumbens slices of chronic desipramine (DMI)- and saline-treated rats were investigated using a superfusion technique. The K +-induced release of [ 3H]DA from nucleus accumbens slices was shown to be Ca 2+-dependent by ascorbic acid. In experiments with isoproterenol, ascorbic acid was added to the superfusion media in order to prevent the otherwise rapid oxidation of the drug. The K +-induced release of [ 3H]DA from nucleus accumbens slices of saline-treated rats was significantly decreased by the α 2-adrenoceptor agonist, clonidine(10 μM; 89 ± 2.4%of control values; P < 0.002), and significantly enhanced by the β-adrenoceptor agonist, isoproterenol(1 and 10 μM; 122 ± 4.3and171 ± 2.9%of control values, P < 0.002andP < 0.001, respectively). The basal release of [ 3H]DA was strongly enhanced by 10 μM but not 1 μM isoproterenol. Chronic DMI pretreatment (10 mg/kg i.p. for 28 days) did not significantly alter the K +-induced release of [ 3H]DA. Chronic DMI treatment attenuated the α-adrenoceptor-mediated inhibition of [ 3H]DA release, while the β-adrenoceptor-mediated stimulation remained unchanged. The net effect of chronic DMI treatment therefore would appear to be a facilitation of dopaminergic neurotransmission in the mesolimbic system. This is consistent with behavioural evidence which suggests that the function of the mesolimbic dopaminergic reward system is facilitated by chronic treatment with antidepressant drugs.

A TRH analog (DN-1417): Motor stimulation with rearing related to catecholaminergic mechanisms in rats

The effect of an analog of TRH, γ-butyrolactone-γ-carbonyl-histidyl-prolinamide citrate (DN-1417) on motor activity was studied in rats. Peripheral administration of DN-1417 (0.2–20 mg kg , i.p.) caused a significant, dose-dependent increase in total spontaneous motor activity, with a definite increase in rearing behaviour. Both increases in spontaneous motor activity and rearing behaviour were markedly inhibited by pretreatment with chlorpromazine (1, 5 mg kg , i.p.), haloperidol (0.1, 0.5 mg kg , i.p.), pimozide (1 mg kg , i.p.) or α-methyltyrosine (250 mg kg , i.p.). Only stimulation of rearing behaviour was selectively attenuated by phenoxybenzamine (5 mg kg , i.p.) or FLA-63 (25 mg kg , i.p.) at doses producing no significant effect on spontaneous motor activity. Although propranolol (10 mg kg , i.p.) and methysergide (10 mg kg , i.p.) had no effect, atropine (10 mg kg , i.p.) and mecamylamine (10 mg kg , i.p.) respectively potentiated and counteracted the effects of DN-1417. Concerning the stimulation of spontaneous motor activity, the nucleus accumbens and lateral hypothalamic area were most sensitive to DN-1417, and the lateral hypothalamic area was the most sensitive site for the stimulation of rearing. Furthermore, DN-1417 (5 × 10 −5 M) significantly enhanced the spontaneous release of [ 3H]dopamine from the rat nucleus accumbens slices in vitro. These findings indicate that the motor stimulatory action of DN-1417 appears to be mediated primarily via a dopaminergic mechanism by enhancing the release of dopamine from nerve terminals, including the nucleus accumbens in the mesolimbic dopamine system, and, in turn, the rearing may be mediated via noradrenergic mechanism.

A thyrotropin releasing hormone analog, DN-1417, increases endogenous dopamine release from slices of rat striatum and nucleus accumbens.

Endogenous dopamine (DA) released from slices of rat striatum and n. accumbens into the superfusate was quantified with high performance liquid chromatography (HPLC) combined with an electrohemical detector (ECD). The basal efflux of DA from slices of rat striatum and n. accumbens were 600 pg/mg protein/10 min and 400 pg/mg protein/10 min, respectively. Compared with normal K+ Krebs-Ringer solution, 25 mM K+ Krebs-Ringer solution significantly incleased (about 20 times) the DA efflux. This stimulant effect of high K+ did not occur in Ca2+ deficient Krebs - Ringer solution. Methamphetamine (10-7 -10-3M) caused significant increases in DA efflux in a dose dependent manner. This system may be quite useful to investigate endogenous DA releasing mechanisms in slices of rat brain. Thyrotropin releasing hormone (10-5 -10-3M) did not increase the DA release from either the n. accumbens or the striatum. On the other hand, DN -1417, γ-butyrolactone-γ-histidyl-prolinamide citrate, caused a significant increase in DA efflux from both regions. Removal of Ca2+ from the Krebs-Ringer solution abolished the effect of DN-1417. The stimulant effect of DN -1417 seemed to be greater in the n. accumbens than in the striatum.

The amphetamine-like releasing effect of the alkaloid (−)cathinone on rat nucleus accumbens and rabbit caudate nucleus

Kalix, Peter: The amphetamine-like releasing effect of the alkaloid (−) cathinone on rat nucleus accumbens and rabbit caudate nucleus. Prog. Neuro-Psychopharmacol. S Biol. Psychiat. 6: 1. (−) Cathinone, a new alkaloid from khat leaves, has recently been reporte to have amphetamine-like behavioral effects. In order to investigate the effects of this compound on the cellular level, slices of rat nucleus accumbens, prelabelled with 3H-dopamine, were superfused with solutions of (−) cathinone. 2. It was found that (−) cathinone, as (+) amphetamine, enhanced the release of radioactivity from rat nucleus accumbens tissue. 3. In similar experiments on rabbit caudate nucleus it was observed that the catecholamine reuptake inhibitors benztropine, nomifensine and mazindol were able to block the (−) cathinone-induced release, indicating that the alkaloid has to penetrate to intraneuronal sites in order to evoke release. 4. It is concluded that the pharmacological similarity between (−) cathinone and (+) amphetamine extends to the cellular level and that the behavioral effects of (−) cathinone are due to stimulation of release from central catecholamine storage sites.

Thyrotrophin releasing hormone stimulates release of [3H]-dopamine from slices of rat nucleus accumbens in vitro.

Thyrotrophin releasing hormone (TRH) (25 to 100 microM) was found to stimulate the efflux of [3Hu-dopamine from small slices of rat nucleus accumbens, but not from similar slices of rat caudate nucleus. Uptake inhibition was not responsible for this action, since at 10 and 50 microM TRH had no effect on the ability of small slices of nucleus accumbens to accumulate radioactivity when incubated with 10(-7) M [3H]-dopamine. In addition the hormone had no effect on basal or dopamine-stimulated adenylate cyclase, nor did it displace [3H]-spiperone binding, in membrane preparations from nucleus accumbens.