Various GABA-mimetic drugs differently affect cocaine-evoked hyperlocomotion and sensitization.
To substantiate the notion that cocaine behavioral effects may be influenced by gamma-aminobutyric acid (GABA) neurotransmission male Wistar rats were injected with gabapentin (a cyclic GABA analogue), tiagabine (a GABA reuptake inhibitor), or vigabatrin (a GABA transaminase inhibitor) before acute or repeated treatment with cocaine evoking either locomotor hyperactivation or sensitization. Gabapentin (1-30 mg/kg), tiagabine (2.5-10 mg/kg) or vigabatrin (75-250 mg/kg) attenuated the cocaine (10 mg/kg)-induced hyperactivation and in the highest doses they also decreased basal locomotor activation. Vigabatrin (75-250 mg/kg) dose-dependently reduced the development of cocaine sensitization in rats treated repeatedly (days 1-5) with cocaine (10 mg/kg) and then challenged with cocaine (10 mg/kg) following 5-day withdrawal; the remaining drugs were ineffective. When injected acutely with a cocaine challenge dose, gabapentin (3-10 mg/kg) or vigabatrin (150 mg/kg), but not tiagabine, significantly attenuated the expression of cocaine sensitization. The present results show that enhanced GABA-ergic neurotransmission exerted inhibitory actions on acute responses to cocaine, however, only in a case of vigabatrin the inhibition seems to be unrelated to the inhibitory effect of the drugs on basal locomotor activity. The finding that vigabatrin protected against the development and the expression of cocaine sensitization further supports its therapeutic potential in the treatment of cocaine dependence.
Filip
Małgorzata
M
Department of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Smetna, Poland. filip@if-pan.krakow.pl
Frankowska
Małgorzata
M
Gołda
Anna
A
Zaniewska
Magdalena
M
Vetulani
Jerzy
J
Przegaliński
Edmund
E
D000588:Amines / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects*; D003042:Cocaine / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000517:prevention & control*; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018682:GABA Agents / Q000494:pharmacology*; D018755:GABA Agonists / Q000494:pharmacology; D000077206:Gabapentin; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D009557:Nipecotic Acids / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D000078308:Tiagabine; D020888:Vigabatrin / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D000588:Amines; D003509:Cyclohexanecarboxylic Acids; D018765:Dopamine Uptake Inhibitors; D018691:Excitatory Amino Acid Antagonists; D018682:GABA Agents; D018755:GABA Agonists; D009557:Nipecotic Acids; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D020888:Vigabatrin; D003042:Cocaine; D000078308:Tiagabine