Rat Nucleus Accumbens Neurons Research Articles

The dopamine D 1 receptor antagonist SCH 23390 can exert D 1 agonist-like effects on rat nucleus accumbens neurons

Interactions between the selective dopamine D 1-class receptor antagonist SCH 23390 and the dopamine D 2-class receptor agonist quinpirole on nucleus accumbens neurons were investigated with extracellular single cell recording and microiontophoresis. Because dopamine D 1 receptor stimulation enables many dopamine D 2 receptor-mediated effects, SCH 23390 was expected to antagonize quinpirole-induced inhibition of activity. Although concurrent iontophoretic administration of SCH 23390 attenuated the inhibitory effects of quinpirole on most neurons, the antagonist further suppressed the firing of most neurons during attempts to reverse quinpirole-induced inhibition. SCH 23390 also reinstated (enabled) quinpirole-induced inhibition in rats acutely depleted of dopamine. These findings suggest that under certain conditions, SCH 23390 may exert dopamine D 1 agonist-like effects.

Dopamine receptor antagonists prevent expression, but not development, of morphine sensitization

The present experiments determined the effects of selective dopamine receptor antagonists on the initiation and expression of sensitization to the locomotor-stimulating effects of morphine in rats. Although both the dopamine D 1 receptor antagonist R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1 H-3-benzazepine hydrochloride (SCH 23390, 0.25 mg/kg) and the dopamine D 2 receptor antagonist eticlopride (0.1 mg/kg) suppressed the ability of morphine (10 mg/kg) to elicit sensitized locomotor activity during the course of a 12 day treatment schedule, subsequent tests with morphine alone revealed significant sensitization. Sensitization in the SCH 23390 + morphine group could not be attributed to dopamine D 1 receptor supersensitivity caused by repeated SCH 23390 administration because electrophysiological recordings indicated that nucleus accumbens neurons in SCH 23390-treated rats were not more sensitive to the inhibitory effects of either dopamine or a dopamine D 1 receptor-selective agonist. Thus, dopamine receptor stimulation may be involved in expression, but not development, of morphine sensitization.

Enhanced responses of nucleus accumbens neurons in male rats to novel odors associated with sexually receptive females

One group of male rats was trained to associate novel odors with three different environmental conditions: the presence of (i) a sexually receptive female (RF), (ii) an unreceptive female (UF) and (iii) no other rat (NO). A second group of males received no training. Single units in nucleus accumbens (NAC) were then recorded in anesthetized animals and their responsiveness to various odors was tested. Odors that had been associated with receptive females during training evoked significantly more unit responses in NAC than did the same odors in untrained males. There were no differences between trained and untrained males in the numbers of units responsive to odors associated with unreceptive females and with the empty training chamber. In trained animals, both the percentage of responding units and the magnitude of olfactory-evoked responses were significantly larger with RF-associated odors than with either UF or NO odors. Both of these effects were more pronounced in rats that had ejaculated with females during training than in rats that had not. Findings demonstrated that pairing odors with the presentation of sexually receptive females enhanced the responsiveness of NAC neurons to those odors and indicated a role for NAC in associating environmental stimuli with natural reward processes.

Relationship between D 1 dopamine receptors, adenylate cyclase, and the electrophysiological responses of rat nucleus accumbens neurons

The electrophysiological effects of three selective D1 dopamine (DA) receptor agonists, which exhibit different potencies and efficacies for stimulation of adenylate cyclase, were compared in the rat nucleus accumbens (NAc) using single unit recording and microiontophoretic techniques. The partial agonists SKF75670 and SKF38393, and the full agonist SKF81297 produced nearly identical current-response curves for the inhibition of firing of NAc neurons. In rats acutely depleted of DA by alpha-methyl-p-tyrosine (AMPT) pretreatment, all three D1 agonists enabled the inhibition of firing produced by the selective D2 receptor agonist quinpirole, with SKF38393 exerting the greatest efficacy, followed by SKF81297 and SKF75670. Thus, no apparent relationship was found between the previously reported ability of these compounds to stimulate cyclic adenosine monophosphate (cAMP) production and their ability either to inhibit the firing of NAc neurons or to enable quinpirole-mediated inhibition of firing in DA-depleted rats. In addition, the membrane-permeable cAMP analog 8-bromo-cAMP also caused a current-dependent inhibition of the firing of NAc neurons, but failed to enable quinpirole-mediated inhibition in AMPT-pretreated animals. These results suggest either that only a small percentage of D1 receptors need to be stimulated to produce these electrophysiological effects, or that D1 receptors exist within the rat NAc which are linked to transduction mechanisms other than, or in addition to, adenylate cyclase.

Cation current activated by hyperpolarization in a subset of rat nucleus accumbens neurons

1. Intracellular recordings were made from neurons in slices of rat nucleus accumbens in vitro. Membrane currents were measured in the potential range -60 to -120 mV with the use of a single-electrode, voltage-clamp amplifier. 2. A minority of neurons (28/285) was identified that had resting membrane potentials almost 20 mV less negative than the majority of the cells. These cells, but not the majority, had an inward current that activated slowly when the cells were hyperpolarized from -60 to -120 mV. The time constant of activation was approximately 3 s at -70 mV and 100 ms at -120 mV. 3. This inward current was completely blocked by external cesium (2 mM) but unaffected by barium. The current was reduced in solutions containing low-sodium concentration and increased in solutions with high-potassium concentration; its reversal potential was estimated to be -36 mV. 4. It is concluded that two types of neuron can be distinguished in the rat nucleus accumbens on the basis of the presence or absence of a cation current activated by hyperpolarization. This current (IH, also called If and IQ) causes the neurons to have less-polarized resting potentials than the majority of nucleus accumbens neurons.

Inward rectification in rat nucleus accumbens neurons

1. Intracellular recordings were made from neurons in slices cut from the rat nucleus accumbens septi. Membrane currents were measured with a single-electrode voltage-clamp amplifier in the potential range -50 to -140 mV. 2. In control conditions (2.5 mM potassium), the resting membrane potential of the neurons was -83.4 +/- 1.1 (SE) mV (n = 157). Steady state membrane conductance was voltage dependent, being 34.8 +/- 1.7 nS (n = 25) at -100 mV and 8.0 +/- 0.7 nS (n = 25) at -60 mV. 3. Barium (1 microM) markedly reduced the inward rectification and caused a small inward current (40.6 +/- 8.7 pA, n = 8) at the resting potential. These effects became larger with higher barium concentrations, and, in 100 microM barium, the current-voltage relation was straight. 4. The block of the inward current by barium (at -130 mV) occurred with an exponential time course; the time constant was approximately 1 s at 1 microM barium and less than 90 ms with 100 microM. Strontium had effects similar to those of barium, but 1000-fold higher concentrations were required. Cesium chloride (2 mM) and rubidium chloride (2 mM) also blocked the inward rectification; their action reached steady state within 50 ms. 5. It is concluded that the nucleus accumbens neurons have a potassium conductance with many features of a typical inward rectifier and that this contributes to the potassium conductance at the resting potential.

Depression by dopamine of the EPSPs in nucleus accumbens neurons of methamphetamine-pretreated rats

Depression by dopamine of the EPSPs in nucleus accumbens neurons of methamphetamine-pretreated rats

Acute effects of methamphetamine applied microiontophoretically to nucleus accumbens neurons in rats

Microiontophoretic studies were performed to elucidate the acute effects of methamphetamine on the nucleus accumbens (Acc) neurons receiving input from the parafascicular nucleus (Pf) of the thalamus using rats anesthetized with chloral hydrate. Spike generation upon Pf stimulation was inhibited by conditioning stimuli applied to the ventral tegmental area (VTA), which is rich in dopamine-containing neurons, and by iontophoretic application of methamphetamine as well as dopamine. The VTA-, methamphetamine- and dopamine-induced inhibition of the spikes elicited by Pf stimulation was antagonized during simultaneous application of haloperidol. Glutamate-induced firing was also inhibited during iontophoretic application of methamphetamine and dopamine in neurons receiving input from the Pf, and the inhibition was blocked by simultaneously applied haloperidol. In the reserpine-treated animals, however, the Pf-induced spikes were not affected by methamphetamine, but inhibited by dopamine. These results indicate that methamphetamine inhibits the Acc neurons receiving input from the Pf, probably by releasing dopamine from dopaminergic nerve terminals from the VTA.

Acute effects of methamphetamine applied microiontophoretically to nucleus accumbens neurons in rats

Microiontophoretic studies were performed to elucidate the acute effects of methamphetamine on the nucleus accumbens (Acc) neurons receiving input from the parafascicular nucleus (Pf) of the thalamus using rats anesthetized with chloral hydrate. Spike generation upon Pf stimulation was inhibited by conditioning stimuli applied to the ventral tegmental area (VTA), which is rich in dopamine-containing neurons, and by iontophoretic application of methamphetamine as well as dopamine. The VTA-, methamphetamine- and dopamine-induced inhibition of the spikes elicited by Pf stimulation was antagonized during simultaneous application of haloperidol. Glutamate-induced firing was also inhibited during iontophoretic application of methamphetamine and dopamine in neurons receiving input from the Pf, and the inhibition was blocked by simultaneously applied haloperidol. In the reserpine-treated animals, however, the Pf-induced spikes were not affected by methamphetamine, but inhibited by dopamine. These results indicate that methamphetamine inhibits the Acc neurons receiving input from the Pf, probably by releasing dopamine from dopaminergic nerve terminals from the VTA.

D-1 dopamine receptor stimulation enables the inhibition of nucleus accumbens neurons by a D-2 receptor agonist

Depletion of catecholamines by pretreatment with the tyrosine hydroxylase inhibitor α-methyl-para-tyrosine attenuated the ability of the selective D-2 dopamine receptor agonist quinpirole to inhibit rat nucleus accumbens neurons when applied directly by microiontophoresis. Concurrent iontophoretic administration of the D-1 selective agonist SKF 38393, at currents which alone produced little inhibition, reinstated the inhibitory effect of quinpirole. These findings suggest that D-1 receptor stimulation may play a necessary ‘enabling’ role for D-2 receptor-mediated functional responses.

Intracellular recordings from rat nucleus accumbens neurons in vitro

Intracellular recordings were obtained from rat nucleus accumbens (NAC) neurons in brain slice preparations. Local stimulations evoked depolarizing postsynaptic potential (DPSP). Injections of low density depolarizing currents decreased the amplitude of the DPSP and reversed a later portion of the DPSP into a hyperpolarizing potential. Superfusion of pentobarbital facilitated the reversal of this later portion of DPSP and bicuculline abolished this polarity reversal. These data suggested that the DPSP evoked by local stimulation consisted of a combination of an excitatory and an inhibitory postsynaptic potential, and that the latter was probably mediated by γ-aminobutyric acid.