Systemic PCP treatment elevates brain extracellular 5-HT: a microdialysis study in awake rats.
THE NMDA receptor antagonist phencyclidine (PCP) has low micromolar affinity for the 5-HT reuptake site, but it is uncertain whether PCP blocks 5-HT reuptake when given systemically to rats in behaviourally stimulating doses. We here report for the first time that systemically administered PCP (5 mg/kg, s.c.) increases extracellular 5-HT levels in the rat medial prefrontal cortex (to 322%) and dorsal hippocampus (to 233%). Increases were found also when citalopram (1 microM) was included in the perfusion medium (to 184 and 180%, respectively). Extracellular 5-HIAA concentrations increased during both conditions, and extracellular GABA decreased in the dorsal hippocampus. It is concluded that systemic PCP treatment elevates extracellular 5-HT levels, probably through mechanisms other than a blockade of 5-HT reuptake.
Martin
P
P
Department of Pharmacology, Göteborg University, Sweden.
Carlsson
M L
ML
Hjorth
S
S
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D015283:Citalopram / Q000008:administration & dosage / Q000494:pharmacology; D015314:Dialysis Solutions / Q000737:chemistry; D004333:Drug Administration Routes; D005110:Extracellular Space / Q000737:chemistry*; D006624:Hippocampus / Q000737:chemistry / Q000187:drug effects; D006897:Hydroxyindoleacetic Acid / Q000032:analysis; D007279:Injections, Subcutaneous; D008297:Male; D017551:Microdialysis; D010477:Perfusion; D010622:Phencyclidine / Q000008:administration & dosage / Q000494:pharmacology*; D017397:Prefrontal Cortex / Q000737:chemistry / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000032:analysis / Q000096:biosynthesis*; D014851:Wakefulness; D005680:gamma-Aminobutyric Acid / Q000032:analysis
D015314:Dialysis Solutions; D015283:Citalopram; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D005680:gamma-Aminobutyric Acid; D010622:Phencyclidine