Differential effects of phencyclidine and methamphetamine on dopamine metabolism in rat frontal cortex and striatum as revealed by in vivo dialysis.
K Nishijima, A Kashiwa, A Hashimoto, H Iwama, Asami Umino, Toru Nishikawa
Synapse (New York, N.Y.) April 1996 DOI: 10.1002/(sici)1098-2396(199604)22:4<304::aid-syn2>3.0.co;2-f (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vivo microdialysis study in rats Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | Phencyclidine Methamphetamine Tetrodotoxin |
| Dose | PCP 2.5-10 mg/kg i.p.; MAP 4.8 mg/kg i.p.; TTX 10(-5) M |
| Key points | PCP increased dopamine and metabolites in the medial frontal cortex dose-dependently but had much weaker effects in the striatum; tetrodotoxin blocked PCP's effects in both regions. The authors suggest PCP raises cortical dopamine mainly by increasing impulse flow in dopamine neurons, while its striatal effect may mainly reflect reuptake inhibition of dopamine released by basal neuron activity. MAP produced large, tetrodotoxin-resistant dopamine increases in both regions, suggesting direct action at dopamine nerve terminals. |
Abstract
We have examined the effects of schizophrenomimetic drugs including phencyclidine (PCP) and methamphetamine (MAP) on cortical and striatal dopamine (DA) metabolism using an in vivo dialysis technique in the rat. An acute systemic injection of PCP (2.5-10 mg/kg, intraperitoneally (i.p.)) dramatically increased concentrations of DA, 3,4-dihydroxy-phenylacetic acid, and homovanillic acid in the dialysates from the medial frontal cortex in a dose-dependent fashion. However, PCP (2.5-10 mg/kg, i.p.) caused a much lower augmentation of extracellular DA release, with a significant decrease in dialysate DOPAC levels in the striatum. Moreover, continuous infusion of tetrodotoxin (TTX, 10(-5) M) into the prefrontal or striatal region through the microdialysis tube completely blocked the ability of PCP (10 mg/kg, i.p.) to alter the extracellular release of DA and its metabolites in the respective areas. In contrast, MAP (4.8 mg/kg, i.p.) elicited a marked and tetrodotoxin-resistant increase in DA levels with a significant loss of DOPAC contents in the extracellular space of both the frontal cortex and the striatum. The present results clearly demonstrate the differential effects of PCP on cortical and striatal DA transmission, suggesting that PCP may facilitate DA release in the medial frontal cortex by increasing impulse flow in the DA neurons projecting to the cortical area, whereas PCP-induced elevation of extracellular DA in the striatum may be caused mainly by reuptake inhibition of DA liberated by basal activity of the striatal DA neurons. The regional variation in PCP-induced DA release would be due to the combination of NMDA (N-methyl-D-aspartate) receptor blocking and DA reuptake inhibition by the drug. The uniform and TTX-resistant nature of MAP-induced changes in brain DA metabolism may result from the direct actions of MAP at DA nerve terminals.