Adenosine A2a receptors in the nucleus accumbens mediate locomotor depression
| Autor: | Robin A. Barraco, M. Parizon, K. A. Martens, Howard J. Normile |
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| Rok vydání: | 1993 |
| Předmět: |
Agonist
Male medicine.medical_specialty Adenosine Microinjections medicine.drug_class Vasodilator Agents Adenosine A2A receptor Adenosine-5'-(N-ethylcarboxamide) Biology Motor Activity Adenosine receptor antagonist Nucleus Accumbens chemistry.chemical_compound Adenosine A1 receptor Mice Internal medicine Phenethylamines medicine Animals Antihypertensive Agents CGS-21680 Mice Inbred ICR Dose-Response Relationship Drug General Neuroscience Receptors Purinergic Adenosine receptor Endocrinology chemistry Depression Chemical DMPX Theobromine medicine.drug |
| Zdroj: | Brain research bulletin. 31(3-4) |
| ISSN: | 0361-9230 |
| Popis: | The effects on locomotor activity (LA) of selective agonists for adenosine receptor subtypes were examined in mice following bilateral injections into the nucleus accumbens (ACB). The ACB is not only richly innervated by dopaminergic (DA) terminals but also exhibits the highest densities of adenosine A 2a receptors in the brain. CGS 21680 (2-[p-(2-carboxyethyl)phenethylamino]-5'-N-ethylcarboxamidoadenosine), a potent and highly selective adenosine A 2a receptor agonist, elicited pronounced, dose-related reductions in LA (ID 50 dosage = 0.0031 nmol/mouse). NECA (5'-N-ethylcarboxamidoadenosine), a mixed adenosine receptor agonist which exhibits high selectivity and potency at striatal A 2a receptors, similarly elicited dose-related reductions in LA (ID 50 dosage = 0.0023 nmol/mouse). In contrast, intra-ACB injections of CFA (N 6 -cyclopentyladenosine), a highly selective agonist for adenosine A 1 receptors, did not exert any significant effects on LA, even at 2.0 nmol/mouse, a dosage at which both CGS 21680 and NECA depressed LA by almost 90% compared to vehicle controls. Further, the pronounced locomotor depression elicited by intra-ACB injections of both CGS 21680 and NECA, at approximately the ID 65 dosage, was significantly antagonized by IP pretreatment with DMPX, (3,7-dimethyl-1-propargylxanthine), an adenosine receptor antagonist with selectivity for A 2 receptors in the striatum, at a dosage (0.15 mmol/mouse) which alone had no significant effect on LA. These observations provide support for the notion that adenosine may selectively modulate DA-mediated mesolimbic behavioral circuits via agonist actions at a population of A 2a receptors densely concentrated in the ventral striatum. |
| Databáze: | OpenAIRE |
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