Acute effects of D-1 and D-2 dopamine receptor agonist and antagonist drugs on basal ganglia [Met5]- and [Leu5]-enkephalin and neurotensin content in the rat.
The effects of acute systemic injection of the D-1 agonist SKF 38393 (2.5-20 mg/kg) or the D-1 antagonist SCH 23390 (0.25-2.0 mg/kg), and of the D-2 agonist quinpirole (0.12-1.0 mg/kg) or the D-2 antagonist sulpiride (25-100 mg/kg) on the neuropeptide content of rat basal ganglia were investigated. In striatum, the [Met5]- and [Leu5]-enkephalin content was unaffected by administration of SKF 38393 or SCH 23390. Quinpirole had no effect on [Met5]- and [Leu5]-enkephalin levels but sulpiride produced an increase in both [Met5]- and [Leu5]-enkephalin content. In the nucleus accumbens, SKF 38393 decreased and SCH 23390 increased [Met5]- and [Leu5]enkephalin levels. Quinpirole decreased [Met5]- and [Leu5]-enkephalin levels, while sulpiride decreased [Leu5]-enkephalin levels alone. The content of [Leu5]- but not [Met5]-enkephalin levels in the substantia nigra was increased by administration of SKF 38393, and decreased by SCH 23390. Quinpirole and sulpiride were without effect on the [Met5]- or [Leu5]-enkephalin content of substantia nigra. Neurotensin levels in striatum were increased by administration of SKF 38393 and decreased by SCH 23390. Similarly, quinpirole decreased the neurotensin content while sulpiride caused an increase. In the nucleus accumbens, the neurotensin content was not affected by administration of SKF 38393 but increased by SCH 23390. Neither quinpirole nor sulpiride altered neurotensin levels in the nucleus accumbens. Neurotensin levels in substantia nigra were unaffected by the administration of SKF 38393 and SCH 23390, or by quinpirole and sulpiride. These results indicate that acute administration of D-1 and D-2 agonist and antagonist drugs can alter the levels of [Met5]- and [Leu5]-enkephalin and neurotensin in basal ganglia. However, there are marked differences between brain regions in the regulation of peptide levels by acute D-1 and D-2 receptor occupation.
Taylor
M D
MD
Parkinson's Disease Society Experimental Research Laboratories, King's College of London, U.K.
de Ceballos
M L
ML
Jenner
P
P
Marsden
C D
CD
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D001479:Basal Ganglia / Q000187:drug effects* / Q000378:metabolism; D001552:Benzazepines / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D015259:Dopamine Agents / Q000008:administration & dosage / Q000494:pharmacology*; D018492:Dopamine Antagonists; D004743:Enkephalin, Leucine / Q000378:metabolism*; D004744:Enkephalin, Methionine / Q000378:metabolism*; D004873:Ergolines / Q000494:pharmacology; D008297:Male; D009496:Neurotensin / Q000378:metabolism*; D019257:Quinpirole; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D013469:Sulpiride / Q000494:pharmacology
D001552:Benzazepines; D015259:Dopamine Agents; D018492:Dopamine Antagonists; D004873:Ergolines; D019257:Quinpirole; D009496:Neurotensin; D004744:Enkephalin, Methionine; D004743:Enkephalin, Leucine; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D013469:Sulpiride