Evidence that LY-141865 specifically stimulates the D-2 dopamine receptor

Tsuruta, K.; Frey, Elizabeth A.; Grewe, C. W.; Côté, Thomas E.; Eskay, Robert L.; Kebabian, John W.

doi:10.1038/292463a0

Cited by 346 publications

(74 citation statements)

References 22 publications

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“…Recently, O'Boyle et al, (1984) showed that SCH-23390 antagonized the effects of RU-24213, a selective D-2 dopamine agonist. In accord with this latter result, the present study clearly demonstrates that in control rats SCH-23390 will antagonize the locomotion induced by LY-171555, another D-2 dopamine agonist (Tsuruta et al, 1981).…”

Section: Discussionsupporting

confidence: 88%

“…The present study examined the action of SCH-23390 against a specific D-2 dopamine agonist, LY-171555 (Tsuruta et al, 1981), in control rats and in 6-OHDA-treated rats (Breese et al, 1985). This investigation provides additional confirmation that SCH-23390 is a weaker inhibitor of D-2 agonist activity than of D-1 agonist effect in 6-OHDA-lesioned rats (Arnt and Hyttel, 1984).…”

Section: Introductionmentioning

confidence: 99%

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SCH-23390 antagonism of a D-2 dopamine agonist depends upon catecholaminergic neurons

Breese

Mueller

1985

European Journal of Pharmacology

100

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SCH-23390, a selective D-1 dopamine antagonist, was found to antagonize the locomotor stimulation induced by LY-171555, an action similar to that for haloperidol in control animals. However, this action of SCH-23390 was prevented in rats treated with 6-hydroxydopamine (6-OHDA) or with reserpine plus α-methyl-tyrosine pretreatment. These results indicate that the action of SCH-23390 to antagonize D-2 dopamine receptor actions is dependent upon functional catecholamine-containing neurons. In contrast to the lack of action of SCH-23390 to antagonize LY-171555 in 6-OHDA-treated rats, SCH-23390 blocked the locomotor stimulation induced by SKF-39393, a D-1 dopamine agonist, after this treatment. Thus, D-1 dopamine receptors are distinct from D-2 receptor sites and can exhibit a behavior similar to that observed when D-2 receptors are stimulated. These data suggest that D-1 receptor sites modulate D-2 dopamine receptor function through a mechanism dependent upon functionally intact catecholaminecontaining neurons.

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Section: Discussionsupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

SCH-23390 antagonism of a D-2 dopamine agonist depends upon catecholaminergic neurons

Breese

Mueller

1985

European Journal of Pharmacology

100

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“…Animal behavior was analyzed 15-30 min after drug infusion in each session, and the location of the implanted cannula was confirmed once the behavioral analysis had been completed. SKF81297 (SKF) and SCH23390 (SCH) were used as a D1 agonist and a D1 antagonist, respectively; whereas quinpirole and eticlopride were used as a D2 agonist and a D2 antagonist, respectively (19)(20)(21)(22).…”

Section: D1-receptor Regulation Of the Direct Pathway In Acquisition Ofmentioning

confidence: 99%

Pathway-specific control of reward learning and its flexibility via selective dopamine receptors in the nucleus accumbens

Yawata

Yamaguchi

Danjo

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

109

135

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In the basal ganglia, inputs from the nucleus accumbens (NAc) are transmitted through both direct and indirect pathways and control reward-based learning. In the NAc, dopamine (DA) serves as a key neurotransmitter, modulating these two parallel pathways. This study explored how reward learning and its flexibility are controlled in a pathway-specific and DA receptor-dependent manner. We used two techniques (i) reversible neurotransmission blocking (RNB), in which transmission of the direct (D-RNB) or the indirect pathway (I-RNB) in the NAc on both sides of the hemispheres was selectively blocked by transmission-blocking tetanus toxin; and (ii) asymmetric RNB, in which transmission of the direct (D-aRNB) or the indirect pathway (I-aRNB) was unilaterally blocked by RNB techniques and the intact side of the NAc was infused with DA agonists or antagonists. Reward-based learning was assessed by measuring goal-directed learning ability based on visual cue tasks (VCTs) or response-direction tasks (RDTs). Learning flexibility was then tested by switching from a previously learned VCT to a new VCT or RDT. D-RNB mice and D1 receptor antagonist-treated D-aRNB mice showed severe impairments in learning acquisition but normal flexibility to switch from a previously learned strategy. In contrast, I-RNB mice and D2 receptor agonist-treated I-aRNB mice showed normal learning acquisition but severe impairments not only in the flexibility to the learning switch but also in the subsequent acquisition of learning a new strategy. D1 and D2 receptors thus play distinct but cooperative roles in reward learning and its flexibility in a pathway-specific manner.goal-directed behavior | perseveration | transmission modulation | neurotransmission blockade | striatal neurons T he basal ganglia are the key neural substrates that control reward-based learning and its flexibility to effectively acquire rewards under changing environmental circumstances (1-3). Dysfunction of the basal ganglia leads to severe cognitive and learning impairments as exemplified in Parkinson's disease, schizophrenia, and drug addiction (4-6). In the basal ganglia circuitry, the projection neurons in the striatum and the nucleus accumbens (NAc), which is the ventral part of the striatum, are divided into two subpopulations, i.e., striatonigral neurons of the direct pathway and striatopallidal neurons of the indirect pathway (1,7,8). The outputs of these two parallel pathways converge at the substantia nigra pars reticulata/ventral tegmental area (VTA) and control the dynamic balance of the basal ganglia-thalamocortical circuitry (1, 9). The two types of the striatal projection neurons are morphologically indistinguishable, but the striatonigral and striatopallidal neurons selectively express D1 and D2 dopamine (DA) receptors (1, 10, 11). This difference in expression profile as well as the distinct ligand affinities of these two DA receptors is thought to be critical for modulating transmission of the pathways involved in rewarding behaviors (3,12). However, whether a...

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“…These rats were subsequently given 3 mg/kg of the D 1 -dopamine agonist SKF-38393 at weekly intervals to assure that maximal locomotor responses were observed (Breese et al 1985b). Rats treated as adults with 6-OHDA were challenged with 0.3 mg/kg of the D 2 -dopamine agonist LY-171555 (Tsuruta et al 1981), and locomotor activity was measured (Breese et al 1984). Only those lesioned rats with a locomotor response greater than 10,000 counts were used in subsequent experiments.…”

Section: Generalmentioning

confidence: 99%

Enhanced muscimol-induced behavioral responses after 6-OHDA lesions: relevance to susceptibility for self-mutilation behavior in neonatally lesioned rats

et al. 1987

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Adult rats lesioned with 6-hydroxydopamine (6-OHDA), either as neonates or as adults, demonstrated increased turning, compared to unlesioned controls, when muscimol was unilaterally microinjected into the substantia nigra reticulata (SNR). At the higher doses of muscimol, the lesioned rats were so intensely lateralized that circling was impeded. These data suggest a functional supersensitivity of receptors associated with GABA function in the SNR of 6-OHDA-lesioned rats. When 30 ng muscimol was administered bilaterally into the SNR, self-mutilation behavior (SMB) was observed in 2/11 of the control unlesioned rats, in 0/8 adult 6-OHDA-lesioned rats, and in 11/11 of the neonatally-lesioned rats tested. The ability of muscimol to produce SMB in the rats lesioned as neonates was dose related. Behavioral observations indicated that behaviors associated with SMB (self-biting and taffy pulling) were present in neonatal, but not adult lesioned rats. Behavioral responses to dopamine agonist administration were also different between rats lesioned as neonates and those lesioned as adults with 6-OHDA. These data support the view that lesions of dopaminergic neurons cause an increased functional responsiveness of receptors acted upon by muscimol in the SNR, and that the increased susceptibility for SMB in neonatally lesioned rats is determined by neurons distal to the GABA receptor complex in the SNR. KeywordsMuscimol; Substantia nigra reticulata; Self-mutilation behavior; 6-Hydroxydopamine-neonatal lesion; 6-Hydroxydopamine-adult lesion; Turning behavior; Behavior, muscimol-induced; SKF-38393; LY-171555; L-dopa; Monoamine metabolites There is considerable evidence implicating dopaminergic mechanisms in motor function (Hornykiewicz 1973). In addition, GABA-containing neurons in the striatum also appear to play a significant role in motor control (Dray 1980;Graybiel and Ragsdale 1983;McGeer et al. 1984). These striatal GABAergic projections have been found to terminate in both segments of the globus pallidus as well as in the zona reticulata of the substantia nigra (SNR) (Fonnum etal. 1978;Preston et al. 1980;Scheel-Kruger et al. 1981). Unilateral administration into SNR of drugs which are associated with GABA receptor function all cause contralateral turning (Scheel-Kruger etal. 1977;Waddington 1978;Waddington and Cross 1979;McDevitt and Yunger 1982). In addition, GABA-mimetics microinjected bilaterally into the SNR or other terminal regions associated with striatal GABA efferents induce behaviors which resemble the effects induced by dopamine. These data led to the hypothesis that GABA efferents from the striatum act as secondary mediators of behaviors triggered by dopamine receptor stimulation (Scheel-Kruger et al. 1977 Waddington 1978a, b).There are several observations suggesting that disruption of the function of GABA efferents from the striatum results in a change in receptor function in the SNR. For example, Pan et al. (1983) found that destruction of GABA efferents increased the number of muscimol binding...

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Evidence that LY-141865 specifically stimulates the D-2 dopamine receptor

Cited by 346 publications

References 22 publications

SCH-23390 antagonism of a D-2 dopamine agonist depends upon catecholaminergic neurons

SCH-23390 antagonism of a D-2 dopamine agonist depends upon catecholaminergic neurons

Pathway-specific control of reward learning and its flexibility via selective dopamine receptors in the nucleus accumbens

Enhanced muscimol-induced behavioral responses after 6-OHDA lesions: relevance to susceptibility for self-mutilation behavior in neonatally lesioned rats

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