Format

Send to

Choose Destination
Psychopharmacology (Berl). 2019 Jul;236(7):2243-2258. doi: 10.1007/s00213-019-05221-3. Epub 2019 Mar 27.

Effects of intrastriatal dopamine D1 or D2 antagonists on methamphetamine-induced egocentric and allocentric learning and memory deficits in Sprague-Dawley rats.

Author information

1
Department of Pediatrics, Div. of Neurology, University of Cincinnati College of Medicine and Cincinnati Children's Research Foundation, Cincinnati, OH, 45229, USA.
2
Department of Pediatrics, Div. of Neurology, University of Cincinnati College of Medicine and Cincinnati Children's Research Foundation, Cincinnati, OH, 45229, USA. charles.vorhees@cchmc.org.

Abstract

RATIONALE:

Methamphetamine (MA) is an abused psychostimulant that causes cognitive deficits after chronic use. Neostriatal dopamine receptors play a role in MA monoamine neurotoxicity. Blocking dopamine receptors prior to MA exposure in adult rats attenuates monoamine reductions and reactive gliosis.

OBJECTIVES:

We tested whether blocking dopamine receptors protects against cognitive deficits.

METHODS:

First, we determined the effects of MA alone versus MA in combination with the dopamine receptor D1 antagonist SCH-23390 or the dopamine receptor D2 antagonist sulpiride on cFos expression and monoamines at the age when rats in the cognitive experiment were to begin testing and monoamines in rats after cognitive testing.

RESULTS:

SCH-23390 infused into the neostriatum prior to systemic administration of MA attenuated MA-induced cFos activation while sulpiride induced cFos activation. Two weeks after MA, rats had dopamine and serotonin reductions that were attenuated by each antagonist. Other rats treated the same way, were tested for egocentric learning and memory in the Cincinnati water maze, for navigational strategy in a star water maze, and spatial learning and memory in a Morris water maze. Pre-treatment with SCH-23390 or sulpiride attenuated the effects of MA on egocentric and spatial learning and memory. MA-treated rats showed a shift from an egocentric to a disorganized strategy in the star maze that was less disorganized in groups receiving MA and an antagonist. Post-behavior monoamine reductions remained but were attenuated by the antagonists but not identically to what was seen in rats not behaviorally tested.

CONCLUSIONS:

The results show for the first time that dopamine receptors are mediators of MA-induced cognitive deficits.

KEYWORDS:

Dopamine D1 antagonist; Dopamine D2 antagonist; Egocentric learning; Methamphetamine; Monoamines; Rat; SCH-23390; Spatial learning; Sulpiride

PMID:
30919007
PMCID:
PMC6626678
[Available on 2020-07-01]
DOI:
10.1007/s00213-019-05221-3

Supplemental Content

Full text links

Icon for Springer
Loading ...
Support Center