The GABA-B antagonist 2-hydroxysaclofen reverses the effects of baclofen on the discriminative stimulus effects of D-amphetamine in the conditioned taste aversion procedure.

Full Abstract

Some of the behavioral effects of d-amphetamine (d-AMPH) are mediated by an increase in dopamine neurotransmission in the nucleus accumbens. However, there is evidence that gamma-amino-butyric-acid-B (GABA-B) receptors are involved in some behavioral effects of D-AMPH and cocaine. Here, we examined the effects of baclofen on the discriminative stimulus properties of D-AMPH, using conditioned taste aversion (CTA) as the drug discrimination procedure. Male Wistar rats were deprived of water and trained in the CTA procedure. They received D-AMPH (1 mg/kg, i.p.) before gaining access to saccharin, which was followed by an injection of LiCl. On alternate days, the subjects received saline before and after the access to saccharin. After the rats learned the D-AMPH-saline discrimination, the standard dose of D-AMPH was replaced by different doses of D-AMPH, baclofen (a GABA-B receptor agonist), 2-hydroxysaclofen (a GABA-B receptor antagonist), a combination of baclofen+D-AMPH, or a combination of 2-hydroxysaclofen+baclofen+D-AMPH. Baclofen did not substitute for D-AMPH, but, when combined with D-AMPH, it produced a small but significant decrease in the discriminative stimulus effects of D-AMPH. This effect was reversed by administration of 2-hydroxysaclofen. These data suggest that GABA-B receptors play a regulatory role in the discriminative stimulus effects of D-AMPH.

Author information

Author/s: Miranda, Florencio (F); Jiménez, Juan C (JC); Cedillo, Laura N (LN); Sandoval-Sánchez, Alma (A); Millán-Mejía, Patricia (P); Sánchez-Castillo, Hugo (H); Velázquez-Martínez, David N (DN);

Affiliation: FES Iztacala, Universidad Nacional Autónoma de México, Av de los Barrios 1, Los Reyes Iztacala Tlalnepantla, Edo. de México 54090, México. fmirandah(-atsign-)yahoo.com

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: Pharmacology, biochemistry, and behavior (Pharmacol Biochem Behav), published in United States. (Language: eng)

Reference: 2009-Jul; vol 93 (issue 1) : pp 25-30

Dates: Created 2009/05/20; Completed 2009/08/19;

PMID: 19361543, status: MEDLINE (last retrieval date: 8/21/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals
Baclofen - analogs & derivatives; pharmacology
Central Nervous System Stimulants - pharmacology
Conditioning (Psychology) - drug effects; physiology
Dextroamphetamine - pharmacology
Discrimination (Psychology) - drug effects; physiology
Disease Models, Animal
GABA Antagonists - pharmacology

GABA Antagonists - pharmacology
Male
Rats
Rats, Wistar
Receptors, GABA-B - antagonists & inhibitors; physiology
Substance-Related Disorders - etiology; physiopathology; psychology
Synaptic Transmission - drug effects; physiology
Taste Perception - drug effects; physiology

Associated Chemicals: Central Nervous System Stimulants (0) ; GABA Antagonists (0) ; Receptors, GABA-B (0) ; Baclofen (1134-47-0) ; 2-hydroxysaclofen (117354-64-0) ; Dextroamphetamine (51-64-9)

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