%0 Journal Article
%T Interactions of a Dopamine D1 Receptor Agonist with Glutamate NMDA Receptor Antagonists on the Volitional Consumption of Ethanol by the mHEP Rat
%A Brian A. McMillen
%A Courtney L. Lommatzsch
%A Michael J. Sayonh
%A Helen L. Williams
%J Pharmaceuticals
%D 2013
%I MDPI AG
%R 10.3390/ph6040469
%X Stimulation of the dopamine D1 receptor is reported to cause the phosphorylation of DARPP-32 at the thre34 position and activates the protein. If intracellular Ca 2+ is increased, such as after activation of the glutamate NMDA receptor, calcineurin activity increases and the phosphates will be removed. This balance of phosphorylation control suggests that a D 1 receptor agonist and a NMDA glutamate receptor antagonist should have additive or synergistic actions to increase activated DARPP-32 and consequent behavioral effects. This hypothesis was tested in a volitional consumption of ethanol model: the selectively bred Myers¡¯ high ethanol preferring (mHEP) rat. A 3-day baseline period was followed by 3-days of twice daily injections of drug(s) or vehicle(s) and then a 3-day post-treatment period. Vehicle, the D 1 agonist SKF 38393, the non-competitive NMDA receptor antagonist memantine, or their combination were injected 2 h before and after lights out. The combination of 5.0 mg/kg SKF 38393 with either 3.0 or 10 mg/kg memantine did not produce an additive or synergistic effect. For example, 5.0 mg/kg SKF reduced consumption of ethanol by 27.3% and 10 mg/kg memantine by 39.8%. When combined, consumption declined by 48.2% and the proportion of ethanol solution to total fluids consumed declined by 17%. However, the consumption of food also declined by 36.6%. The latter result indicates that this dose combination had a non-specific effect. The combination of SKF 38393 with (+)-MK-801, another NMDA receptor antagonist, also failed to show an additive effect. The lack of additivity and specificity suggests that the hypothesis may not be correct for this in vivo model. £¿The interaction of these different receptor systems with intraneuronal signaling and behaviors needs to be studied further.
%K glutamate receptors
%K consumatory behaviors
%K DARPP-32
%U http://www.mdpi.com/1424-8247/6/4/469