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K M Kantak

Publications and source records attributed to K M Kantak.

At least 19 recordsLinked to original sources
PubMed1992

Acute and multiple injection effects of magnesium on responding maintained by cocaine, extinction from cocaine, glucose + saccharin, and food.

In a variety of behavioral experiments, magnesium has effects that are similar to cocaine and other psychomotor stimulants. Of particular relevance to the present experiments is the recent finding that magnesium maintains responding in cocaine-trained rats. It would be expected, therefore, that injections of magnesium would alter the rate of responding maintained by self-administered cocaine in rats. Five experiments examined the specificity and selectivity of this interaction. Acute and multiple injections of MgCl2 (15-250 mg/kg) produced dose-dependent reductions in responding maintained by cocaine (0.1-2 mg/kg/infusion). Testing for acute injection effects occurred following injections, while testing for multiple injection effects occurred prior to daily injections. Doses of 30 and 125 mg/kg MgCl2 reduced responding maintained by doses of cocaine that were below the training dose of 0.75 mg/kg/infusion. MgCl2 in a dose of 250 mg/kg markedly suppressed responding maintained by each dose of cocaine. A magnesium-deficient diet produced a dose-dependent increase in responding maintained by 0.1 mg/kg/infusion cocaine. In order to determine the specificity and selectively of these effects, acute and multiple injections of MgCl2 were examined on glucose + saccharin- and food-maintained responding. The acute effects of MgCl2 injections were specific because food-maintained responding was not affected, except by the highest dose of 250 mg/kg. This demonstrates that lever pressing was not nonspecifically reduced by 30 and 125 mg/kg MgCl2 during cocaine availability. However, the effects on cocaine-maintained responding were not selective for cocaine because glucose + saccharin-maintained responding and responding during extinction from cocaine were affected by MgCl2 in a manner similar to cocaine-maintained responding.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Magnesium-maintained self-administration responding in cocaine-trained rats.

Magnesium chloride (MgCl2) produces behavioral effects similar to those of psychomotor stimulants in a variety of behavioral situations. Because MgCl2 appears to have stimulant properties, the ability of MgCl2 to maintain responding in a rat self-administration paradigm was examined in seven experiments under different access and schedule conditions in cocaine-trained rats. These varied from the availability of MgCl2 for a single day's test session subsequent to 1 h availability of cocaine, to the availability of MgCl2 for 10 or 20 days after cocaine availability was totally discontinued. Fixed ratio 1, fixed ratio 5, and progressive ratio 1, 2 and 3 schedules of drug delivery were used. The results demonstrate that MgCl2 may substitute for self-administered cocaine because it maintained responding; it did so dose dependently to maintain a constant level of MgCl2 intake; and it did so over a 10-day period of time both with and without access to cocaine on test days. Responding maintained by MgCl2 when cocaine was no longer available was similar under fixed ratio 1 and 5 schedule conditions. The progressive ratio breakpoints for MgCl2 were significantly higher than those for saline, but significantly lower than those for cocaine. These data indicate that MgCl2 has some reinforcing efficacy in cocaine-trained rats, particularly under fixed ratio 1 and 5 schedules, but has a low abuse potential compared to cocaine.

Animals↗
PubMed1990

Failure of magnesium to maintain self-administration in cocaine-naive rats.

Previous research has shown that magnesium interacts with cocaine in such a way that it potentiates its action in a variety of behavioral situations. More recently, it has been demonstrated that magnesium will dose dependently substitute for cocaine self-administration and reduce the intake of cocaine. It is of considerable interest to determine if magnesium would be self-administered in cocaine-naive animals. The results of two experiments demonstrate that magnesium is not self-administered by cocaine-naive rats since although responding for magnesium chloride is above hypertonic saline control levels on day 1 of access, this responding is not maintained on subsequent days, does not occur in a regularly spaced pattern over time, and is not inversely related to dose. Taken together these data indicate that magnesium is a substitute for cocaine that has low abuse potential.

Animals↗
PubMed1990

Enhancement of apomorphine and l-amphetamine-induced behaviors by magnesium.

The behavioral effects of magnesium suggest that this divalent cation has psychomotor stimulant-like properties. Because deficiencies of this cation lead to reductions in drug-induced behaviors dependent on the levels of norepinephrine and dopamine, and numerous in vitro studies have demonstrated a relationship between magnesium and catecholamine activity, the present experiments investigate whether administration of magnesium will lead to increases in stereotyped and locomotor behaviors induced by apomorphine and l-amphetamine. Such changes would suggest that magnesium is increasing the activity of catecholamines in vivo. The results demonstrate that magnesium dose dependently increases the potency of these drugs by producing greater behavioral effects at certain drug doses, by producing shifts to the left in dose-response functions, and by producing decreases in the ED50 as dose of magnesium increases.

Amphetamine↗
PubMed1990

Postconditioning effects of magnesium on cocaine conditioned place preference in mice.

Magnesium chloride (MgCl2) has recently been shown to have stimulant-like properties. Because stimulants are known to induce conditioned place preference (CPP), the CPP procedure was used to test the hypothesis that cocaine and MgCl2 share similar stimulus properties. This would be shown if cocaine-induced CPP could be enhanced in a postconditioning preference test by MgCl2 and other stimulants. Mice were conditioned with 5.0 mg/kg cocaine to the nonpreferred end of a three-compartment straight shuttle box. All groups showed significant shifts in preference from the preconditioning test to the postconditioning test. There were no changes in place preference over test days in mice that were injected only with saline and therefore not conditioned. When animals were given acute injections of either saline, 5.0 mg/kg cocaine, 1.0 mg/kg amphetamine, 30 mg/kg MgCl2, 10 mg/kg pentobarbital, or 0.25 mg/kg haloperidol following conditioning with cocaine, amphetamine and MgCl2 elevated the conditioned cocaine effect, and pentobarbital and haloperidol decreased the conditioned cocaine effect compared to saline. In addition, there was a dose-dependent influence of MgCl2, with 30 mg/kg producing the maximum effect on the conditioned cocaine effect.

Animals↗
PubMed1990

Magnesium-induced conditioned place preference in mice.

A conditioned place preference procedure was used in mice to test the hypothesis that magnesium possesses reinforcing properties. Mice were conditioned to the nonpreferred end of a three-compartment straight shuttle box with MgCl2 injections alternating with saline injections on the preferred end. Dose of MgCl2 was varied (0, 15, 30, 125 mg/kg) as well as number of conditioning trials (8 or 16). On the day after the first postconditioning test, animals were given acute injections of 5 mg/kg cocaine, or other test drug, to determine if the conditioned effect on behavior would be potentiated, maintained or blocked by these test drugs. Results demonstrated that 15 mg/kg MgCl2 induced the greatest amount of conditioning and that increasing the number of MgCl2/place pairings did not enhance the amount of conditioning, but rather, it decreased it. Amphetamine potentiated MgCl2-induced place preference; cocaine and pentobarbital maintained it; and haloperidol blocked it. These data indicate that MgCl2 has some primary reinforcing properties in mice and that MgCl2 shares stimulus properties with other stimulants and reinforcing substances.

Animals↗
PubMed1989

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.

Aggression↗
PubMed1988

Social, motor, and autonomic signs of morphine withdrawal: differential sensitivities to catecholaminergic drugs in mice.

Drugs that predominantly influence catecholamines were used in order to simultaneously determine their ability to alter salient signs of social, motor and autonomic activity during morphine withdrawal, and to compare the sensitivity of each of these signs to these drugs. Cocaine, d-amphetamine, apomorphine and L-dopa increased attack and threat, but did not induce defensive behavior in morphine-withdrawn resident mice who were more responsive to the aggression-enhancing effects of these drugs than placebo control mice. Concurrently measured withdrawal jumping was not affected by these drugs, and the sensitivity to the hypothermic effects of these drugs was reduced. In contrast, clonidine decreased attack and threat behaviors, and morphine-withdrawn mice were more sensitive to this inhibitory influence. But like the stimulant drugs, clonidine did not affect withdrawal jumping, and the hypothermic action of clonidine was attenuated in morphine-withdrawn mice. These findings show that in mice, opiate withdrawal leads to altered attack and threat that is further amplified by catecholaminergic drugs. The present pattern of results indicates differential drug effects on social, motor and autonomic functions when the behaviors are measured 48 h following withdrawal.

Animals↗
PubMed1988

Magnesium deficiency alters aggressive behavior and catecholamine function.

Magnesium is an abundant mineral in the brain and is important for monoamine neurotransmitter synthesis and receptor binding. It should, therefore, have behavior-altering effects. Three experiments were conducted to determine the influence of magnesium deficiencies on aggressive behavior and catecholamine function in mice. There were concentration- and time-dependent reductions in offensive aggressive behavior with magnesium deficiencies. Defensive behavior was affected in a manner opposite to that of offensive behavior. Upon administration of low doses of apomorphine and l-amphetamine, less dopamine- and norepinephrine-related behavior occurred with less magnesium in the diet. These reductions also showed a time dependency. These data demonstrate that magnesium has an influence on aggressive behavior in mice. Also, a magnesium deficiency is capable of altering the potency of catecholamine stimulating drugs.

Aggression↗
PubMed1986

Aggression during morphine withdrawal: effects of method of withdrawal, fighting experience, and social role.

Offensive and defensive components of aggressive behavior were determined in resident and intruder mice. Withdrawal aggression was measured after the removal of a subcutaneous morphine pellet or after precipitation by naloxone in naive mice and after removal of a morphine pellet in mice with prior fighting experience. In naive mice, removal of a morphine pellet led to increases in attack bites and threats but naloxone-precipitated withdrawal led to decreases in these behaviors and to increases in defensive posturing, escape attempts and vocalizations. Prior fighting experience abolished the enhanced attack behaviors of resident mice following morphine pellet removal, but led to heightened defensive behavior in intruder mice. The behavior of intruder mice appeared more sensitive to naloxone administration than the behavior of resident mice; naloxone influenced not only intruder defensive behavior, but also other non-aggressive behaviors. The social role of the drug recipient and his prior history of aggressive behavior are important determinants of morphine and naloxone effects on aggression.

Aggression↗
PubMed1986

Stimulant-like effects of magnesium on aggression in mice.

The effects of magnesium excesses resulting from daily injections of magnesium chloride (MgCl2) were examined on offensive behavior in a resident-intruder situation. Male mice tested 5 min post-injection of 15 mg/kg or 30 mg/kg exhibited a significantly greater number of attacks and threats than saline controls; while in mice injected with 125 mg/kg threat and attack behaviors were decreased. No tolerance developed to this decrease which persisted throughout the 15 day injection period. Tolerance to the aggression enhancing effects developed in the 30 mg/kg group which returned to normal by Day 4 and in the 15 mg/kg group which returned to normal by Day 15. Two weeks following the last injection, all groups performed equally. When mice were tested prior to daily injections on Days 4, 8, and 15 in a second experiment, there were no MgCl2 dose differences in threat or attack behavior, thus there was no cumulative effect of MgCl2 on behavior. These data and our previous data showing that MgCl2 deficiencies reduce offensive aggression suggest an inverted U-shape function to magnesium's influence on behavior. Since aggression has been linked to the neurotransmitters dopamine, norepinephrine, and serotonin, and magnesium has been shown to be an important cofactor in the activity of these neurotransmitters, it is possible that the effects seen here are related to changes in one or more of these systems.

Aggression↗
PubMed1984

Regional changes in monoamines and metabolites following defensive aggression in the rat.

Pharmacological studies have demonstrated that shock-induced defensive fighting is modulated by manipulations of the serotonergic, noradrenergic and dopaminergic neurotransmitter systems. In the present study, regional changes in 5- hydroxytryptamine , norepinephrine, dopamine and their metabolites 5-hydroxyindoleacetic acid, 3-methoxy-4-hydroxyphenylethylene glycol and 3,4-dihydroxyphenylacetic acid were measured following shock-induced fighting using high performance liquid chromatography coupled with electrochemical detection. Fighting produced reductions in the serotonergic, noradrenergic and dopaminergic systems and elevations in the noradrenergic and dopaminergic systems within the brain stem, hypothalamus, hippocampus, caudate and amygdala relative to shocked or non-shocked controls. These data demonstrate that the activities of these neurotransmitters are involved in defensive aggression in rats. The changes in catecholamines may indicate adaptive responses to stress, while the changes in serotonin may indicate a permissive function for serotonin depletion in defensive fighting.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1981

Facilitation of shock-induced fighting following intraventricular 5,7-dihydroxytryptamine and 6-hydroxydopa.

Using a 15-s intershock interval, an increase in shock-induced fighting was observed following intraventricular 96 microgram 5,7-dihydroxytryptamine (5,7-DHT) and 90 microgram 6-hydroxydopa (6-OHdopa). The incidence of predatory mouse killing was enhanced by 5,7-DHT, but was not affected by 6-OHdopa. Pain sensitivity was increased by 6-OHdopa, but both neurotoxins produced hyperreactivity to footshock. Specific serotonin depletion was produced by 5,7-DHT and norepinephrine depletion by 6-OHdopa. The increase in shock-induced fighting could not be predicted on the basis of monoamine depletion alone, since a long intershock interval was necessary to observe this increase.

5,7-Dihydroxytryptamine↗