Low-dose effect of ethanol on locomotor activity induced by activation of the mesolimbic system.
Four experiments were designed to study the ability of 0.5 g/kg ethanol (EtOH) intraperitoneally to modify locomotor activity induced by drugs that interact with different sites in the mesolimbic system (MLS) of male Sprague-Dawley rats. Locomotor activity was measured in a doughnut-shaped circular arena after various treatments. EtOH alone did not alter locomotor activity in any of the experiments. Amphetamine (AMP, intraperitoneally or intraaccumbens) increased locomotor activity in a dose-dependent manner, and the presence of EtOH attenuated AMP-induced locomotor activity. Bilateral infusion of GABAA antagonist picrotoxin (PIC) into the ventral tegmental area also increased locomotor activity in a dose-dependent manner, and the presence of EtOH attenuated PIC-induced locomotor activity. On the other hand, the interaction between bilateral infusion of mu-receptor agonist Tyr-D-Ala-Gly-NMe-Phe-Gly-ol (DAGO) and EtOH on locomotor activity is complex. The highest dose of DAGO that significantly increased locomotor activity was not affected by the presence of EtOH. But, with lower doses of DAGO that either had no effect or a small increase in locomotor activity, the combination of EtOH and DAGO increased and attenuated locomotor activity, respectively. Results from this study support our hypothesis that a low dose of EtOH that does not modify behavior can interact with neurotransmitter systems in the brain and modify drug-induced locomotor activity. Modification of this drug-induced locomotor activity by a low dose of EtOH is dependent on the rate of ongoing locomotor behavior induced by drug and the neurotransmitter substrate that the drug modified to induce locomotor behavior.(ABSTRACT TRUNCATED AT 250 WORDS)
Milton
G V
GV
Department of Pharmacology and Toxicology, College of Pharmacy, University of Texas at Austin, USA.
Randall
P K
PK
Erickson
C K
CK
D000661:Amphetamine / Q000494:pharmacology; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001143:Arousal / Q000187:drug effects*; D015259:Dopamine Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology*; D018756:GABA Antagonists / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D008032:Limbic System / Q000187:drug effects*; D008297:Male; D008636:Mesencephalon / Q000187:drug effects*; D009043:Motor Activity / Q000187:drug effects*; D009434:Neural Pathways / Q000187:drug effects; D009714:Nucleus Accumbens / Q000187:drug effects; D010852:Picrotoxin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000187:drug effects; D011963:Receptors, GABA-A / Q000187:drug effects; D017450:Receptors, Opioid, mu / Q000187:drug effects
D000661:Amphetamine; D000700:Analgesics; D015259:Dopamine Agents; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins; D000431:Ethanol; D018756:GABA Antagonists; D010852:Picrotoxin; D011954:Receptors, Dopamine; D011963:Receptors, GABA-A; D017450:Receptors, Opioid, mu