Glutamate antagonists modify the motor stimulant actions of D1 and D2 agonists in reserpine-treated mice in complex ways that are not predictive of their interactions with the mixed D1/D2 agonist apomorphine
In 24 h reserpine-treated mice, the locomotion induced by the D1 dopamine agonist SKF 38393 (30 mg/kg IP) was facilitated by the NMDA antagonists MK 801 (0.4 mg/kg IP), CPP (1 mg/kg IP), CGP 40116 (1 mg/kg IP) and HA 966 (2 mg/kg IP), and by the AMPA antagonist NBQX (0.2 mg/kg IP). By contrast, CPP, CGP 40116 and NBQX had no effect on, while MK 801 and HA 966 suppressed, the locomotion elicited by the selective D2 agonist RU 24213 (5 mg/kg SC). When these same doses of glutamate antagonists were tested against the locomotion induced by a threshold (0.025 mg/kg SC), intermediate (0.1 mg/kg SC) or large dose (0.5 mg/kg SC) of the mixed D1/D2 agonist apomorphine, CPP, CGP 40116 and HA 966 were found to have no significant effect, whilst MK 801 was strongly inhibitory and NBQX potentiated the response to 0.1 mg/kg apomorphine only. It is evident from these data that the behavioural interaction profiles between glutamate antagonists and dopamine agonists are complex and depend on the receptor selectivities of the drugs concerned. The manner of the interaction between these glutamate antagonists and selective D1 or D2 agonists, is not predictive of the way that blockade of glutamate transmission interferes with the actions of drugs which have combined D1 and D2 motor stimulant properties.
KeywordsLocomotion mouse reserpine dopamine agonist NMDA antagonist AMPA antagonist
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- Davies J, Evans RH, Herrling PL, Jones AW, Olverman HJ, Pook P, Watkins JC (1986) CPP, a new potent and selective NMDA antagonist. Depression of central neuron responses, affinity for [3H]D-AP5 binding sites on brain membranes and anticonvulsant activity. Brain Res 382: 169–173CrossRefPubMedGoogle Scholar
- Lieberman A, Neophytides A, Leibowitz M, Kupersmith M, Pact V, Walker R, Zasorin N, Goodgold A, Goldstein M (1980) The use of two new dopamine agonists: pergolide and lisuride in Parkinson's disease. In: Rinne UK, Klingler M, Stamm G (eds) Parkinson's disease: current progress, problems and management. Elsevier, Holland, pp 335–361Google Scholar
- Mitchell IJ, Clarke CE, Boyce S, Robertson RG, Peggs D, Sambrook MA, Crossman AR (1989) Neural mechanisms underlying parkinsonian symptoms based upon regional uptake of 2-deoxyglucose in monkeys exposed to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Neuroscience 32: 213–226CrossRefPubMedGoogle Scholar
- Seeman P (1981) Brain dopamine recetpors. Pharmacol Rev 32: 229–313Google Scholar
- Starr MS, Starr BS (1993a) Comparison of the effects of NMDA and AMPA antagonists on the locomotor activity induced by selective D1 and D2 dopamine agonists in reserpine-treated mice. Psychopharmacology (in press)Google Scholar
- Starr MS, Starr BS (1993b) Facilitation of D1 but not D1/D2-dependent locomotion by glutamate antagonists in the reserpine-treated mouse. Eur J Pharmacol (in press)Google Scholar
- Wong EHF, Kemp JA, Priestly T, Knight AR, Woodruff GN, Iversen LL (1988) The anticonvulsant MK-801 is a potent N-methyl-D-aspartate antagonist. Proc Natl Acad Sci 83: 7104Google Scholar