Endogenous and exogenous dopamine depress EPSCs in rat nucleus accumbens in vitro via D1 receptors activation.

Abstract

Birw-inltghazt B15 2TT, UK 1. Whole-cell patch clainp recordings were made fiom nucleus accumbens neurones in slices of rat ventral forebrain. In the presence of piciotoxin (50 /tM), the amplitude of 6-cyano-7-nitroquinoxaline-2,3-dione-sensitive glutamate EP8Cs, recorded at holding potentials between -80 and -90 mV, was reversibly reduced by 56 + 11 % (ra = 6) by dopamine (30 AM). The selective dopamine D1 receptor agonists SKF 38393 (10 AM) and SKF 81297A (10 /tM), but not the selective D2 receptor agonist quinpirole (10 /LM), also reversibly depressed the EPSC by 36-48%. The depression of the EPSC by dopamine was completely blocked by the D1 receptor antagonist SCH 23390 (1 /M), whereas the D2 antagonist (-)-sulpiride (1 pm) was,without effect. 2. EPSCs were reversibly depressed by the dopamine mimetic psychostimulants cocaine(1-20 ,UM) and amphetamine (10-30 ,tM) bv 40 + 16 and 62 + 9%, respectively, but only in about half of the cells tested (11/23 and 6/13, respectively). Their actions were comnpletely reversed b1y SCH 23390 (1 /LM), indicating that endogenous dopamnine can also depress the EPSC via D1 receptors. 3. No discernable effects of dopamnine, SKF 81297A, SKF 38393, quinpirole, cocaine or amphetamine were observed on membrane conductance oIr holding current (at holding potentials of -80 to -90 mV), suggesting that the depression of the EPSC was solelv due to an action on presynaptic D1 receptors. 4. In contrast, agents that elevate intracellular levels of adenosine-3': 5'-cvclic monophosphate (cAMP) (forskolin (1-10 /tM), 3-isobutyl-1-mnethylxanthine (0 1-1 mM), rolipram (10 LM), and dibutyryl cAMP (0-5-1 mM)) caused a reversible increase in the EPSC amplitude (ly 21-150%/O). Furtherinore, in the presence of forskolin (10 /tM), the ability of dopamine to depress synaptic transinission was unaffected.5. Together these data suogest that both exogenous dopamine and dopamnine released fioni intrinsic nerve terminals attenuate glutaimate receptor-mediated synaptic transmission in the nucleus accumbens by presynaptic D1 receptor activation. The transduction mechanism undeilyino this effect does not appear to involve the formation of cAMP.

Modulation of Inhibitory Transmission by Dopamine in Rat Basal Forebrain Nuclei: Activation of Presynaptic D1-like Dopaminergic Receptors

“…Furthermore, our pharmacological studies revealed that the action of DA was mediated via the activation of presynaptically located D 1 -like receptors. Similar reduction of excitatory transmission mediated by presynaptic D 1 -like receptors has been reported in nucleus accumbens (Pennartz et al, 1992;Harvey and Lacey, 1996;Nicola et al, 1996). In contrast, information regarding the effect of DA on inhibitory synaptic transmission in basal forebrain is sparse, although it has been known that iontophoretic application of DA attenuated the inhibitory action of iontophoretically administered GABA on the firing rates of neurons within the globus pallidus (Bergstrom and Walters, 1984).…”

Dopaminergic Modulation of Prefrontal Cortical Input to Nucleus Accumbens NeuronsIn Vivo

“…Stimulation of the VTA in vivo or activation of dopamine receptors in vitro attenuates the responses of accumbens neurons to stimulation of the amygdala or hippocampus (Yang and Mogenson, 1984;Yim and Mogenson, 1988;Charara and Grace, 2003). The amplitude of PFC-evoked EPSPs is also decreased after application of dopamine agonists in vitro (Pennartz et al, 1992;O'Donnell and Grace, 1994;Harvey and Lacey, 1996). Thus, as proposed by Mogenson et al (1988), the primary function of dopamine in the nucleus accumbens appears to be to modulate the effects of excitatory limbic and cortical inputs rather than to drive neuronal activity directly (O'Donnell, 1999;Nicola et al, 2000).…”

“…Although previous in vitro experiments have reported a selective modulation of PFC inputs to the accumbens by a D 1 -like mechanism (Pennartz et al, 1992;Harvey and Lacey, 1996;Nicola et al, 1996), we found no evidence for a role of D 1 receptors in the suppression of prefrontal inputs in vivo, using a selective D 1 antagonist (SCH 23390) at a dose that effectively attenuates responses to VTA stimulation in PFC pyramidal neurons (Lewis and O'Donnell, 2000) or, in conjunction with a D 2 antagonist, in accumbens neurons (Goto and O'Donnell, 2001). Differences between recording conditions, specific antagonists, and/or placement of recording and stimulating electrodes could account for these disparities.…”

“…Such a dissociation may explain why the attenuation of PFC responses can be partially blocked by D 2 antagonism alone, whereas the plateau depolarization in response to VTA train stimulation is shortened only by combined D 1 and D 2 receptor blockade (Goto and O'Donnell, 2001). In vitro experiments, which allow for a more thorough investigation of presynaptic and postsynaptic mechanisms, have supported a presynaptic locus of action for dopamine in modulating synaptic responses, because accumbens neurons do not show consistent changes in input resistance or postsynaptic currents after application of dopamine (O'Donnell and Grace, 1994;Harvey and Lacey, 1996;Nicola et al, 1996). Although dopaminergic afferents do not make clear axoaxonic synaptic contacts on excitatory terminals in the nucleus accumbens (Sesack and Pickel, 1992), dopamine may diffuse extrasynaptically (Garris et al, 1994) to act at receptors reportedly localized on descending cortical terminals in the nucleus accumbens and striatum (Tarazi and Baldessarini, 1999).…”

“…Synaptic responses in accumbens neurons driven by stimulation of either the amygdala or the hippocampus are attenuated by stimulation of the VTA or local iontophoretic application of dopamine in vivo (Yang and Mogenson, 1984;DeFrance et al, 1985;Yim and Mogenson, 1988). Excitatory accumbens responses to PFC stimulation are also decreased by direct application of dopaminergic receptor agonists in vitro (Pennartz et al, 1992;O'Donnell and Grace, 1994;Harvey and Lacey, 1996;Nicola et al, 1996). However, the effects of dopamine and/or activation of the ascending dopaminergic fibers on PFC synaptic responses have not yet been investigated in vivo.…”