Intracerebral baclofen administration decreases amphetamine-induced behavior and neuropeptide gene expression in the striatum

Wenxia Zhou; Adam W Mailloux; Jacqueline F McGinty

doi:10.1038/sj.npp.1300635

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Intracerebral baclofen administration decreases amphetamine-induced behavior and neuropeptide gene expression in the striatum

Journal article

Open access

Peer reviewed

Intracerebral baclofen administration decreases amphetamine-induced behavior and neuropeptide gene expression in the striatum

Wenxia Zhou, Adam W Mailloux and Jacqueline F McGinty

Neuropsychopharmacology (New York, N.Y.), Vol.30(5), pp.880-890

05/2005

DOI: 10.1038/sj.npp.1300635

PMID: 15592348

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Abstract

In a previous study, systemic administration of the GABA(B) receptor agonist, R-(+)-baclofen (2.5 mg/kg, i.p.) blocked acute amphetamine (2.5 mg/kg, i.p.)-induced rearing and neuropeptide (preprodynorphin (PPD), preprotachykinin (PPT), preproenkephalin (PPE), and secretogranin II (SGII)) mRNA expression in the striatum (Zhou et al, 2004). The purpose of the present study was to investigate the site(s) of action of these baclofen effects in the dorsal and ventral striatal circuitries. Infusion of baclofen (75 ng/side) into the ventral tegmental area (VTA), substantia nigra (SN), nucleus accumbens (NA), caudate-putamen (Cpu), or medial prefrontal cortex (mPFC) had no effect on behavioral activity in saline-treated rats habituated to a photocell apparatus. However, intra-VTA infusion of baclofen (75 ng/side) completely blocked, whereas intra-NA and intra-SN infusion of baclofen attenuated, amphetamine-induced vertical activity without affecting amphetamine-induced total distance traveled. In contrast, intramedial PFC and intra-CPu infusion of baclofen had no effect on behavioral activity in amphetamine-treated rats. Infusion of baclofen into the VTA, NA, or SN decreased amphetamine-induced neuropeptide gene expression in the striatum. These results indicate that GABA(B) receptor stimulation within the ventral striatal circuitry is involved in mediating acute amphetamine-induced behaviors and neuropeptide gene expression in the dorsal and ventral striatum. The present study provides information on the potential targets in the brain for baclofen in the initial behavioral and genomic response to amphetamine.

Amphetamine - antagonists & inhibitors

Amphetamine - pharmacology

Animals

Baclofen - administration & dosage

Baclofen - pharmacology

Behavior, Animal - drug effects

Central Nervous System Stimulants - antagonists & inhibitors

Central Nervous System Stimulants - pharmacology

GABA Agonists - administration & dosage

GABA Agonists - pharmacology

Gene Expression - drug effects

In Situ Hybridization

Male

Microinjections

Neostriatum - drug effects

Neostriatum - metabolism

Neuropeptides - biosynthesis

Neuropeptides - genetics

Prefrontal Cortex - physiology

Putamen - physiology

Rats

Rats, Sprague-Dawley

Substantia Nigra - physiology

Details

Title: Subtitle: Intracerebral baclofen administration decreases amphetamine-induced behavior and neuropeptide gene expression in the striatum
Creators: Wenxia Zhou - Medical University of South Carolina
Adam W Mailloux - Medical University of South Carolina
Jacqueline F McGinty - Medical University of South Carolina
Resource Type: Journal article
Publication Details: Neuropsychopharmacology (New York, N.Y.), Vol.30(5), pp.880-890
DOI: 10.1038/sj.npp.1300635
PMID: 15592348
NLM abbreviation: Neuropsychopharmacology
ISSN: 0893-133X
eISSN: 1740-634X
Grant note: DA03982 / NIDA NIH HHS
Language: English
Date published: 05/2005
Academic Unit: Microbiology and Immunology
Record Identifier: 9984297326502771

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