Behavioral effects of dopamine agonists and antagonists in MPTP-lesioned D3 receptor knockout mice
| Autor: | Maria Reploge, Alex V. Yarkov, Diane Hanger, Jeffrey N. Joyce |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Male
Apomorphine Dopamine Agents Clinical Biochemistry Toxicology Biochemistry Levodopa Mice Behavioral Neuroscience chemistry.chemical_compound Cocaine Receptor Mice Knockout Membrane Glycoproteins Behavior Animal MPTP Carbidopa 1-Methyl-4-phenyl-1 2 3 6-tetrahydropyridine Dopamine Agonists Autoreceptor Female medicine.drug Agonist medicine.medical_specialty medicine.drug_class Nerve Tissue Proteins Motor Activity Dopamine agonist Dopamine receptor D3 Dopamine receptor D2 Internal medicine Oxazines medicine Animals Benzopyrans Pyrroles Biological Psychiatry Pharmacology Dopamine Plasma Membrane Transport Proteins Receptors Dopamine D2 Receptors Dopamine D3 Membrane Transport Proteins Grooming Mice Inbred C57BL Endocrinology chemistry Autoradiography Dopamine Antagonists Radiopharmaceuticals Stereotyped Behavior |
| Zdroj: | Pharmacology Biochemistry and Behavior. 76:551-562 |
| ISSN: | 0091-3057 |
| DOI: | 10.1016/j.pbb.2003.09.011 |
| Popis: | To test the modulatory role of D 3 receptors in normal and dopamine-depleted mice, D 3 receptor KO mice and wild-type (WT) littermates were administered saline, l -dopa/carbidopa (20/2 mg/kg ip), a preferential D 3 >D 2 agonist S32504, a D1+D 2 /D 3 agonist apomorphine, a selective D 3 antagonist S33084, or apomorphine with S33084 prior to and after administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). We monitored lines crossed in a 55-min session, average number of rears, and average number of grooming bouts. MPTP treatment produced equivalent 70% losses of dopamine fibers in the caudate putamen (CPu) and nucleus accumbens (NAC) of WT and D 3 KO mice as compared to their control (vehicle injected) counterparts. D 3 receptors were absent in KO mice, and the number of D 3 receptors was unaffected by MPTP-induced loss of DA terminals in WT mice. The results support a lack of involvement of the D 3 receptor for D1:D2 receptor-mediated behavioral activity (synergy). First, S32504 inhibited all behaviors and to a similar degree in D 3 KO and WT mice. Second, S33084 at the higher concentration increased number of lines crossed in response to high dose apomorphine in both D 3 KO and WT mice. Third, in nonlesioned mice, apomorphine-induced gnawing stereotypies were inhibited by S33084 in both D 3 KO and WT mice. Interestingly, the inhibition of apomorphine-induced gnawing was not apparent in MPTP-lesioned mice, and this stereotypy was elevated in D 3 KO-MPTP-lesioned mice. Thus, the suppressive effects of S32504 could be via D2 autoreceptor inhibition of DA release, and D2 receptor blockade by S33084 leads to release of that inhibition. This may be more apparent in MPTP-lesioned partially DA denervated mice. |
| Databáze: | OpenAIRE |
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