Differential effects of haloperidol on phencyclidine‐induced reduction in substance P contents in rat brain regions

Differential effects of haloperidol on phencyclidine‐induced reduction in substance P contents... We investigated the effects of a schizophrenomimetic drug, phencyclidine (PCP), on substance P (SP) contents in the discrete rat brain areas using an enzyme‐immunoassay for SP. The acute intraperitoneal (i.p.) administration of PCP (10 mg/kg), which is a noncompetitive antagonist of the N‐methyl‐D‐aspartate (NMDA) type glutamate receptor and a dopamine uptake inhibitor, reduced the concentration of the peptide in the prefrontal cortex, limbic forebrain, striatum, and substantia nigra, but not in the ventral tegmental area, at 60 or 120 min postinjection. A selective noncompetitive NMDA antagonist, dizocilpine hydrogen maleate ((+)‐MK‐801) (1 mg/kg, i.p.), also caused a decrease in the SP content in the prefrontal cortex and limbic forebrain but failed to alter the content in the other areas studied 30 min thereafter. Dopamine agonists, methamphetamine (4.8 mg/kg, i.p.) and apomorphine (4.4 mg/kg, i.p.), diminished the SP contents in the striatum and substantia nigra 60 min after their injection without effects in the prefrontal cortex, limbic forebrain, and ventral tegmental area. Furthermore, pretreatment with haloperidol (1 mg/kg, i.p.), a D2 preferable dopamine receptor antagonist and a typical antipsychotic, blocked the ability of PCP to decrease the SP concentrations in the substantia nigra but not in the prefrontal cortex. PCP, therefore, might diminish the SP levels by NMDA receptor‐mediated and dopamine‐independent mechanisms in the prefrontal cortex and limbic forebrain, but by NMDA receptor‐independent and dopamine‐dependent mechanisms in the striatum and substantia nigra. The haloperidol‐insensitive reduction of the frontal SP could be involved in certain neuroleptic‐resistant symptoms of PCP‐treated animals, PCP psychosis, or schizophrenia. Synapse 35:292–299, 2000. © 2000 Wiley‐Liss, Inc. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Synapse Wiley

Differential effects of haloperidol on phencyclidine‐induced reduction in substance P contents in rat brain regions

Loading next page...
 
/lp/wiley/differential-effects-of-haloperidol-on-phencyclidine-induced-reduction-M0LtB1Jf2e
Publisher
Wiley
Copyright
Copyright © 2000 Wiley‐Liss, Inc.
ISSN
0887-4476
eISSN
1098-2396
DOI
10.1002/(SICI)1098-2396(20000315)35:4<292::AID-SYN7>3.0.CO;2-3
pmid
10657039
Publisher site
See Article on Publisher Site

Abstract

We investigated the effects of a schizophrenomimetic drug, phencyclidine (PCP), on substance P (SP) contents in the discrete rat brain areas using an enzyme‐immunoassay for SP. The acute intraperitoneal (i.p.) administration of PCP (10 mg/kg), which is a noncompetitive antagonist of the N‐methyl‐D‐aspartate (NMDA) type glutamate receptor and a dopamine uptake inhibitor, reduced the concentration of the peptide in the prefrontal cortex, limbic forebrain, striatum, and substantia nigra, but not in the ventral tegmental area, at 60 or 120 min postinjection. A selective noncompetitive NMDA antagonist, dizocilpine hydrogen maleate ((+)‐MK‐801) (1 mg/kg, i.p.), also caused a decrease in the SP content in the prefrontal cortex and limbic forebrain but failed to alter the content in the other areas studied 30 min thereafter. Dopamine agonists, methamphetamine (4.8 mg/kg, i.p.) and apomorphine (4.4 mg/kg, i.p.), diminished the SP contents in the striatum and substantia nigra 60 min after their injection without effects in the prefrontal cortex, limbic forebrain, and ventral tegmental area. Furthermore, pretreatment with haloperidol (1 mg/kg, i.p.), a D2 preferable dopamine receptor antagonist and a typical antipsychotic, blocked the ability of PCP to decrease the SP concentrations in the substantia nigra but not in the prefrontal cortex. PCP, therefore, might diminish the SP levels by NMDA receptor‐mediated and dopamine‐independent mechanisms in the prefrontal cortex and limbic forebrain, but by NMDA receptor‐independent and dopamine‐dependent mechanisms in the striatum and substantia nigra. The haloperidol‐insensitive reduction of the frontal SP could be involved in certain neuroleptic‐resistant symptoms of PCP‐treated animals, PCP psychosis, or schizophrenia. Synapse 35:292–299, 2000. © 2000 Wiley‐Liss, Inc.

Journal

SynapseWiley

Published: Mar 15, 2000

References

You’re reading a free preview. Subscribe to read the entire article.


DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

Search

Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly

Organize

Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.

Access

Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

DeepDyve

Freelancer

DeepDyve

Pro

Price

FREE

$49/month
$360/year

Save searches from
Google Scholar,
PubMed

Create folders to
organize your research

Export folders, citations

Read DeepDyve articles

Abstract access only

Unlimited access to over
18 million full-text articles

Print

20 pages / month

PDF Discount

20% off