D1 dopamine receptor stimulation enables the postsynaptic, but not autoreceptor, effects of D2 dopamine agonists in nigrostriatal and mesoaccumbens dopamine systems

Abstract

Possible functional interactions between D1 and D2 dopamine (DA) receptors were examined using extracellular single-cell recording with microiontophoretic application of selective D1 and D2 receptor agonists both postsynaptically, in the rat nucleus accumbens (NAc) and caudate-putamen (CPu), and presynaptically, at impulse-regulating somatodendritic DA autoreceptors in the ventral tegmental area (A10) and substantia nigra pars compacta (A9). In addition, synthesis-modulating nerve terminal DA autoreceptors were studied in both the CPu and NAc using the gamma-butyrolactone (GBL) neurochemical model of isolated nerve terminal autoreceptor function in vivo. In both the NAc and CPu, the inhibition of neurons produced by iontophoresis of the D2 receptor agonists quinpirole or RU-24213 was attenuated by acute DA depletion via the tyrosine hydroxylase inhibitor alpha-methyl-p-tyrosine (AMPT). However, during iontophoresis of the selective D1 DA receptor agonist SKF 38393, the inhibitory effects of the D2 agonists were again evident, suggesting that the attenuation of D2 agonist-induced inhibition was due to decreased D1 receptor activation. In contrast, the inhibitory effects produced by the non-selective D1/D2 agonist apomorphine or by SKF 38393 were unaffected by AMPT pretreatment. Thus, D1 receptor activation appears necessary for D2 receptor-mediated inhibition of NAc and CPu neurons, whereas D2 receptor activation is not required for the inhibition produced by D1 receptor stimulation. In contrast to postsynaptic D2 receptors, the ability of DA agonists to stimulate D2 DA autoreceptors was not altered by manipulations of D1 receptor occupation. Enhancing D1 receptor stimulation with SKF 38393 or reducing D1 receptor occupation with either the selective D1 receptor antagonist SCH 23390 or AMPT failed to alter the rate-inhibitory effect of i.v. quinpirole on A9 or A10 DA neurons. Similarly, iontophoresis of SKF 38393 failed to alter the inhibitory effects of iontophoretic quinpirole. SKF 38393 also failed to affect the inhibition of GBL-induced increases in DOPA accumulation (tyrosine hydroxylase activity) produced by quinpirole in either the NAc or CPu. Furthermore, reversal of GBL-induced increases in DOPA accumulation by apomorphine or quinpirole was unaffected by pretreatment with SCH 23390. Therefore, D1 receptor occupation appears to be necessary for the expression of the functional effects of postsynaptic D2 receptor stimulation but not presynaptic D2 DA autoreceptor stimulation.

Striatal dopamine–NMDA receptor interactions in the modulation of glutamate release in the substantia nigra pars reticulata in vivo: opposite role for D1 and D2 receptors

“…Thus, disinhibition of the striatopallidal pathway induced by D 2 receptor blockade may require functional D 1 receptors. The finding that excitation of pallidal neurons induced by D 2 agonists (via inhibition of the striatopallidal projection) is impaired reducing striatal D 1 receptor occupancy (Walters et al 1987;Wachtel et al 1989) further supports this view.…”

Negative Feedback Regulation of Nigrostriatal Dopamine Release: Mediation by Striatal D1 Receptors

“…Previous studies have demonstrated cooperativity between D1 and D2 receptors (White, 1987;Wachtel et al, 1989;Keefe and Gerfen, 1995). At "normal", i.e., basal, DA concentrations, D2 autoreceptors may mediate the inhibition of DA neurons.…”

Lack of Self-Administration of Cocaine in Dopamine D1Receptor Knock-Out Mice

“…For example, both pharmacological blockade and gene knock-out of the dopamine D 1 receptor attenuated the physiological effects of dopamine and D 1 -and D 2 -selective agonists Clark and White, 1987;Walters et al, 1987;White et al, 1988;Wachtel et al, 1989;Johansen et al, 1991;Xu et al, 1994a,b;Cooper et al, 1998;Waszczak et al, 2002). Conversely, D 1 stimulation enabled the full expression of behavioral effects and molecular and cellular adaptations induced by dopamine indirect and direct D 1 and D 2 agonists White et al, 1988;Xu et al, 1994a,b;Gerfen et al, 1995;Keefe and Gerfen, 1995;Xu et al, 2000;RalphWilliams et al, 2002;Waszczak et al, 2002;Fetsko et al, 2003;Zhang et al, 2004;Ralph and Caine, 2005;Zhang et al, 2005;Zhang et al, 2006).…”