Magnesium alters the potency of cocaine and haloperidol on mouse aggression

Magnesium has been shown to have certain behavioral effects similar to the stimulants cocaine and amphetamine, particularly on mouse resident-intruder aggression. Consequently, it was hypothesized that magnesium should interact with the indirect agonist cocaine and the antagonist haloperidol to alter their potency in the mouse resident-intruder model. Acute and chronic drug effects were compared. Results demonstrate an enhancement of cocaine potency by 30 and 125 mg/kg MgCl2 and a lowering of cocaine potency by a 15% required-Mg2+ deficient diet as measured by shifts in the dose response to acutely administered cocaine. Following chronic 0.5 mg/kg cocaine for 15 days, a dose of 125 mg/kg acutely administered MgCl2 prevented the disruptive effects of chronic cocaine on mouse aggression. Acutely administered haloperidol was influenced by Mg2+ treatments in a manner opposite from the effects on cocaine, while the chronic effects of haloperidol were affected in the same manner by Mg2+ treatments as those shown for chronic cocaine. Several mechanisms are suggested to explain these interactions.