The effects of progabide (SL 76002) on locomotor activity and conditioned place preference induced by d-Amphetamine

Scala, Georges Di; Martin‐Iverson, Mathew T.; Phillips, Anthony G.; Fibiger, Hans C.

doi:10.1016/0014-2999(85)90069-x

Cited by 36 publications

(12 citation statements)

References 12 publications

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“…of amphetamine (Di Scala et al, 1985). However, it is difficult to compare this finding to the present as there were differences in rat strains, GABAergic compounds and drugs used to elicit CPP.…”

Section: Discussionmentioning

confidence: 57%

A novel strategy for the treatment of cocaine addiction

Dewey

Morgan

Ashby

et al. 1998

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Cocaine's addictive liability has been linked to its pharmacologic actions on mesotelencephalic dopamine (DA) reinforcement/reward pathways in the central nervous system (CNS). Dopaminergic transmission within these pathways is modulated by gamma-aminobutyric acid (GABA). With this knowledge, we examined the utility of gamma vinylGABA (GVG), a selective and irreversible inhibitor of GABA-transaminase (GABA-T) known to potentiate GABAergic inhibition, to alter cocaine's biochemical effects as well as its effects on behaviors associated with these biochemical changes. GVG significantly attenuated cocaine-induced increases in neostriatal synaptic DA in the non-human primate (baboon) brain as assessed by positron emission tomography (PET) and abolished both the expression and acquisition of cocaine-induced conditioned place preference (CPP). It had no effect on CPP for a food reward, the delivery of cocaine to the brain or locomotor activity. These findings suggest the possible therapeutic utility in cocaine addiction of a pharmacologic strategy targeted at the GABAergic neurotransmitter system, a system distinct from but functionally linked to the DA mesotelencephalic reward/reinforcement system. However, rather than targeting the GABA receptor complex with a direct GABA agonist, this novel approach with GVG takes advantage of the prolonged effects of an irreversible enzyme inhibitor that raises endogenous GABA levels without the addictive liability associated with GABA agonists acting directly at the receptor itself. Human trials with GVG are currently being developed to directly examine the utility of this novel strategy for the treatment of cocaine addiction.

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Section: Discussionmentioning

confidence: 57%

A novel strategy for the treatment of cocaine addiction

Dewey

Morgan

Ashby

et al. 1998

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182

135

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“…For example, progabide attenuates the locomotor effects of cocaine but does not effect cocaine's influence on CPP (Di Scala et al 1985). Conversely, haloperidol attenuates the locomotor stimulation produced by methylphenidate, but does not affect the CPP produced by the drug (Mithani et al 1986).…”

Section: Discussionmentioning

confidence: 95%

Food-deprivation increases cocaine-induced conditioned place preference and locomotor activity in rats

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Sc³

et al. 1997

Psychopharmacology

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Food-deprivation increases the reinforcing efficacy of cocaine and other drugs within self-administration experiments. In this study, the effects of food-deprivation on cocaine-induced conditioned place preference were investigated. Male Sprague-Dawley rats were assigned to one of two feeding conditions: satiated (with ad libitum food) or deprived (maintained at 80% of free-feeding body weights). During conditioning trials, on alternate days, rats received IP injections of cocaine (0.0, 2.5, 5.0, or 10.0 mg/kg; n = 12 per dose group) and were confined for 30 min in one of two distinct environments. On intervening days, the same rats were injected with saline and confined for 30 min in the opposite environment. After four cocaine and four saline trails, a 15-min choice test (with no injections) was given. During this time, the rats were able to move freely through a passageway between both environments. Relative to the food-satiated rats, the food-deprived rats showed a greater conditioned preference for the cocaine-paired environment during the choice test, greater cocaine-induced locomotor activity during conditioning trials, and a greater degree of sensitization to the activating effects of cocaine across conditioning trials. This study extends the general findings of food deprivation-induced increases in the reinforcing efficacy of cocaine to include the conditioned place preference paradigm.

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“…Di Scala et al (1985) found that progabide attenuated the locomotor stimulant effect of amphetamine without affecting CPP learning. Similarly, Mithani et al (1986) were able to dissociate the inhibitory effects of haloperidol on locomotor stimulant effects of methylphenidate from its failure to block a CPP produced by methylphenidate.…”

Section: Discussionmentioning

confidence: 99%

“…However, although there is a relationship between drugs that produce CPP and increased activity, some studies have dissociated these effects. Di Scala et al (1985) found that the GABA mimetic drug progabide attenuated the locomotor stimulant effect of amphetamine but did not influence the CPP produced by the drug. Similarly, Mithani et al (1986) found that the dopamine receptor antagonist haloperidol greatly attenuated the locomotor stimulation produced by methylphenidate, but did not affect the CPP prouced by this drug.…”

mentioning

confidence: 99%

Independence of amphetamine reward from locomotor stimulation demonstrated by conditioned place preference

1988

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The conditioned place preference (CPP) paradigm is used widely as a measure of a drug's rewarding properties. The present study examined whether the CPP produced by amphetamine is dependent on the locomotor stimulation that is produced by the drug. An earlier study (Swerdlow and Koob 1984) found that interfering with locomotor stimulation using restraint during the drug treatment blocked CPP. The present study examined whether this effect of restraint was indeed due to restriction of locomotion or was due to restraint maintaining the stimulus novelty of the CPP apparatus. The first experiment showed that novelty of the apparatus itself was a potent factor in the CPP paradigm and was capable of producing a place preference. The second experiment showed that restraint alone could produce a CPP, as would be expected if it maintained stimulus novelty of the apparatus. It also showed that although a CPP to amphetamine could be blocked by restraining the animals during drug treatment, prior habituation to the apparatus to reduce stimulus novelty before treatment negated the effect of restraint on amphetamine CPP. These results indicate that rats can demonstrate a CPP produced by amphetamine even when their activity is restrained. This suggests that the drug's rewarding properties are not dependent on locomotor stimulation.

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The effects of progabide (SL 76002) on locomotor activity and conditioned place preference induced by d-Amphetamine

Cited by 36 publications

References 12 publications

A novel strategy for the treatment of cocaine addiction

A novel strategy for the treatment of cocaine addiction

Food-deprivation increases cocaine-induced conditioned place preference and locomotor activity in rats

Independence of amphetamine reward from locomotor stimulation demonstrated by conditioned place preference

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