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Low-dose effect of ethanol on locomotor activity induced by activation of the mesolimbic system
G V Milton1, P K Randall, C K Erickson
1Department of Pharmacology and Toxicology, College of Pharmacy, University of Texas at Austin, USA.
Abstract:
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)
Insights
Low doses of ethanol (EtOH) can alter drug-induced locomotor activity by interacting with brain neurotransmitter systems. The effect of EtOH on amphetamine or picrotoxin-induced activity was dose-dependent.
Area of Science:
- Neuroscience
- Pharmacology
- Behavioral Science
Background:
- The mesolimbic system (MLS) is crucial for regulating locomotor activity.
- Ethanol (EtOH) can influence neurotransmitter systems, but its effects on drug-induced behaviors at low doses are not fully understood.
Purpose of the Study:
- To investigate how a low dose of EtOH (0.5 g/kg) modifies locomotor activity induced by drugs targeting the MLS.
- To determine if EtOH's modulatory effects depend on the specific neurotransmitter system or the baseline locomotor activity.
Main Methods:
- Experiments were conducted on male Sprague-Dawley rats using a circular arena to measure locomotor activity.
- Rats were treated with EtOH alone, various drugs (amphetamine, picrotoxin, DAGO) alone, or combinations of EtOH and these drugs.
- Drugs were administered intraperitoneally or via bilateral infusion into the ventral tegmental area.
Main Results:
- EtOH alone did not affect locomotor activity.
- EtOH attenuated locomotor activity induced by amphetamine and picrotoxin.
- EtOH's interaction with DAGO-induced locomotor activity was complex, with effects varying based on DAGO dose.
Conclusions:
- A low, behaviorally inactive dose of EtOH can interact with brain neurotransmitter systems to modify drug-induced locomotor activity.
- The modulatory effect of EtOH is dependent on the rate of ongoing drug-induced behavior and the specific neurotransmitter system involved.