title: Effects of D-amphetamine and phencyclidine on behavior and extracellular concentrations of neurotensin and dopamine in the ventral striatum and the medial prefrontal cortex of the rat.
abstract: The effects of systemically administered phencyclidine (PCP; 2.5 mg/kg, s.c.) and D-amphetamine (1.5 mg/kg, s.c.) on the extracellular concentrations of neurotensin-like immunoreactivity (NT-LI) and dopamine (DA) in the ventral striatum (vSTR) and the medial prefrontal cortex (mPFC) were studied in freely moving rats using microdialysis. In separate animals, the effects of PCP and D-amphetamine on open field activity were also analyzed. PCP, but not D-amphetamine, caused a significant increase (156% over baseline) of NT-LI levels in the vSTR which was relatively short lasting, i.e., of less than 2 h duration. In contrast, both drugs significantly increased NT-LI concentrations in the mPFC by almost 100% during the same period. PCP and D-amphetamine also significantly increased extracellular levels of DA in the vSTR by 83 and 364%, respectively. However, the peak effect of PCP on DA appeared later than that of D-amphetamine, i.e., at 150 and 60 min, respectively, after drug administration. Also in the mPFC, both PCP and D-amphetamine significantly increased DA concentrations by 98 and 284%, respectively. Generally, effects on DA levels of both PCP and D-amphetamine were, in contrast to their effects on NT-LI levels, clearly more long-lasting, i.e., of 3-4 h duration. Behaviorally, D-amphetamine produced a more pronounced, general activation than PCP, with a faster onset of activation, i.e. within 30 vs 90 min after administration. However, both drugs produced long-lasting effects on the spatial organization of behavioral activity, which lasted for 3-4 h. In conclusion, the more pronounced behavioral stimulation by D-amphetamine (1.5 mg/kg, s.c.) vs PCP (2.5 mg/kg, s.c.) in the rat may largely be explained by its more potent DA-releasing effect in the brain. Initial behavioral suppression by PCP, e.g., of rearing, as well as its rather poor locomotor stimulant action in general, might relate to release of NT in the vSTR. The long-lasting, behavioral disorganization by both PCP and D-amphetamine may, however, be related to increased release of DA rather than NT in the mesolimbocortical areas.
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: P
authors.initials: P
authors.lastname: Hertel
authors.forename: J M
authors.initials: JM
authors.lastname: Mathé
authors.forename: G G
authors.initials: GG
authors.lastname: Nomikos
authors.forename: M
authors.initials: M
authors.lastname: Iurlo
authors.forename: A A
authors.initials: AA
authors.lastname: Mathé
authors.forename: T H
authors.initials: TH
authors.lastname: Svensson
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001923:Brain Chemistry / Q000187:drug effects*; D003913:Dextroamphetamine / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D015259:Dopamine Agents / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D008124:Locomotion / Q000187:drug effects; D008297:Male; D017551:Microdialysis; D009043:Motor Activity / Q000187:drug effects; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism; D009496:Neurotensin / Q000378:metabolism; D010622:Phencyclidine / Q000494:pharmacology*; D011180:Postmortem Changes; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D015259:Dopamine Agents; D018691:Excitatory Amino Acid Antagonists; D009496:Neurotensin; D010622:Phencyclidine; D003913:Dextroamphetamine; D004298:Dopamine