PMID- 19629448
OWN - NLM
STAT- MEDLINE
DCOM- 20100114
LR  - 20211020
IS  - 1432-2072 (Electronic)
IS  - 0033-3158 (Linking)
VI  - 206
IP  - 4
DP  - 2009 Nov
TI  - Serotonergic lesions of the dorsal hippocampus differentially modulate locomotor 
      hyperactivity induced by drugs of abuse in rats: implications for schizophrenia.
PG  - 665-76
LID - 10.1007/s00213-009-1617-1 [doi]
AB  - RATIONALE: Psychotomimetic drug-induced locomotor hyperactivity is a widely used 
      animal model of psychotic states, such as in schizophrenia. We previously found 
      that serotonergic lesions of the dorsal, but not ventral, hippocampus in rats 
      result in enhanced phencyclidine-induced locomotor hyperactivity. OBJECTIVES: The 
      objective of this study was to investigate the effect of serotonin depletion in 
      the dorsal and ventral hippocampus on hyperlocomotion induced by ketamine, 
      cocaine, 3,4-methylenedioxymethampethamine (MDMA), methamphetamine, and D: 
      -amphetamine. MATERIALS AND METHODS: Male Sprague-Dawley rats were bilaterally 
      microinjected with vehicle or the serotonergic neurotoxin, 
      5,7-dihydroxytryptamine (5,7-DHT), into the dorsal or ventral hippocampus using a 
      stereotaxic approach. Separate cohorts of rats were used for each drug of abuse; 
      each rat received saline and a low, medium, and high dose of the drug in a 
      random-sequence, repeated-measures protocol. Locomotor hyperactivity following 
      treatment was measured using automated photocell cages. RESULTS: Similar to 
      phencyclidine, 5,7-DHT-induced lesions of the dorsal hippocampus enhanced 
      ketamine-induced hyperlocomotion at all doses. They also reduced 
      methamphetamine-induced hyperlocomotion at the high dose only and caused a minor, 
      biphasic modulation of responses to cocaine. Locomotor responses to D: 
      -amphetamine and MDMA were unchanged by lesions of the dorsal hippocampus. 
      Serotonergic lesions of the ventral hippocampus did not significantly alter 
      locomotor hyperactivity induced by any of the drugs investigated. CONCLUSIONS: 
      These findings further implicate a role for serotonin in the dorsal hippocampus 
      in modulating the behavioral effects of dissociative anesthetics, such as 
      ketamine, with more subtle effects on psychostimulant drugs of abuse. The dorsal 
      hippocampus may be a site of serotonergic dysfunction in aspects of 
      schizophrenia.
FAU - Adams, Wendy
AU  - Adams W
AD  - Behavioural Neuroscience Laboratory, Mental Health Research Institute of 
      Victoria, 155 Oak Street, Parkville, VIC 3052, Australia.
FAU - Ayton, Scott
AU  - Ayton S
FAU - van den Buuse, Maarten
AU  - van den Buuse M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090723
PL  - Germany
TA  - Psychopharmacology (Berl)
JT  - Psychopharmacology
JID - 7608025
RN  - 0 (Amphetamines)
RN  - 31363-74-3 (5,7-Dihydroxytryptamine)
RN  - 333DO1RDJY (Serotonin)
RN  - 690G0D6V8H (Ketamine)
RN  - I5Y540LHVR (Cocaine)
RN  - J1DOI7UV76 (Phencyclidine)
SB  - IM
MH  - 5,7-Dihydroxytryptamine/toxicity
MH  - Amphetamines/administration & dosage/toxicity
MH  - Animals
MH  - Cocaine/administration & dosage/toxicity
MH  - Disease Models, Animal
MH  - Dose-Response Relationship, Drug
MH  - Hippocampus/drug effects/*pathology
MH  - Hyperkinesis/*chemically induced
MH  - Ketamine/administration & dosage/toxicity
MH  - Male
MH  - Phencyclidine/toxicity
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Schizophrenia/*physiopathology
MH  - Serotonin/*metabolism
EDAT- 2009/07/25 09:00
MHDA- 2010/01/15 06:00
CRDT- 2009/07/25 09:00
PHST- 2008/12/08 00:00 [received]
PHST- 2009/07/08 00:00 [accepted]
PHST- 2009/07/25 09:00 [entrez]
PHST- 2009/07/25 09:00 [pubmed]
PHST- 2010/01/15 06:00 [medline]
AID - 10.1007/s00213-009-1617-1 [doi]
PST - ppublish
SO  - Psychopharmacology (Berl). 2009 Nov;206(4):665-76. doi: 
      10.1007/s00213-009-1617-1. Epub 2009 Jul 23.