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Blockade of central neuropeptide Y (NPY) Y2 receptors reduces ethanol self-administration in rats
A Thorsell1, R Rimondini, M Heilig
1Neurotec, Karolinska Institutet, M46, Huddinge University Hospital, SE-141 86 Huddinge, Sweden.
Abstract:
Activation of central neuropeptide Y (NPY) receptors is known to produce several behavioral effects, including feeding, modulation of memory and antagonism of behavioral effects of stress. In addition, experiments in knock-out and transgenic mice have suggested a possible role of NPY regulation of voluntary ethanol intake. NPY receptors involved in this action are not known. Here, we examined the effects of a selective NPY-Y2 receptor antagonist, BIIE0246, on operant responding for ethanol in a sweetened solution, or the sweetened solution without ethanol, during 30 min sessions of free choice between the two. BIIE0246 produced a robust suppression of responding for ethanol (40% reduction, P=0.013) at an intracerebroventricular dose of 1.0 nmol, but not 0.3 nmol. Responding for the saccharin solution was not significantly affected. The dose range examined was selected since preliminary experiments with doses of 3 nmol and higher indicated sedative effects, but such effects were absent up to 1.0 nmol, as shown by unaffected exploratory locomotor activity. In summary, antagonism at central NPY-Y2 receptors seems to selectively suppress operant self-administration of ethanol. This suggests that Y2 receptors might be candidate targets for developing novel pharmacological treatments of alcoholism.
Insights
Antagonizing neuropeptide Y-Y2 (NPY-Y2) receptors selectively reduced voluntary ethanol intake in mice. This finding suggests NPY-Y2 receptors as potential targets for novel alcoholism treatments.
Area of Science:
- Neuroscience
- Pharmacology
- Behavioral Science
Background:
- Central neuropeptide Y (NPY) receptors influence feeding, memory, and stress responses.
- Previous studies suggest NPY may regulate voluntary ethanol consumption, but the specific receptors involved are unknown.
Purpose of the Study:
- To investigate the role of NPY-Y2 receptors in regulating ethanol self-administration.
- To determine if selective NPY-Y2 receptor antagonism affects operant responding for ethanol.
Main Methods:
- Administered a selective NPY-Y2 receptor antagonist (BIIE0246) intracerebroventricularly in mice.
- Assessed operant responding for ethanol or a saccharin solution during free-choice sessions.
- Monitored locomotor activity to assess sedative effects.
Main Results:
- A dose of 1.0 nmol of BIIE0246 significantly suppressed operant responding for ethanol by 40% (P=0.013).
- Lower doses (0.3 nmol) did not affect ethanol intake.
- Responding for the saccharin solution was unaffected, indicating selectivity.
- Locomotor activity remained normal at effective doses, ruling out sedation.
Conclusions:
- Central NPY-Y2 receptor antagonism selectively reduces voluntary ethanol self-administration.
- NPY-Y2 receptors are potential therapeutic targets for developing novel pharmacological treatments for alcoholism.