Locomotor response of nialamide pretreated old rats to intraaccumbens dopamine.

The objective of this study was to determine the locomotor activity response of young (6 month), mature (15 month), and old (26 month) rats to bilateral intraaccumbens injections of dopamine after pretreatment with nialamide. Young and mature rats responded to dopamine with high rates of activity, while old rats either did not respond at all or responded with a lower intensity of activity. In contrast, the response of old rats to dopamine or ergometrine alone or to dopamine after pargyline pretreatment was not less than that of mature and young rats. These results suggest that the attenuated response of old rats to dopamine after nialamide pretreatment is not due to a decrease in dopamine receptor activity, but appears to be due to some unique property of nialamide in these animals. However, the reduced response of old rats to dopamine was not due to the inability of nialamide to inhibit monoamine oxidase, since nialamide completely inhibited the activity of this enzyme in the nucleus accumbens of old rats.

Effect of nialamide on the metabolism of dopamine injected into the nucleus accumbens of old rats.

We have reported previously that after nialamide pretreatment there is an age-related difference in the stimulation of locomotor activity produced by the injection of dopamine bilaterally into the nucleus accumbens. Thus, the stimulation of locomotor activity produced by dopamine in old rats was significantly less than that of young and mature rats. The purpose of the present study was to determine whether nialamide was an effective inhibitor of the metabolism of dopamine after dopamine was injected into the nucleus accumbens of old rats. When we measured the concentration of injected dopamine in the limbic forebrain (nucleus accumbens and olfactory tubercle) of young (6 months), mature (15 months) and old (26 months) rats pretreated with nialamide, the amount of dopamine that was present was significantly less in old rats than in young or mature rats. Consistent with this observation, the concentrations of the dopamine metabolites, homovanillic acid and dihydroxyphenylacetic acid were higher in nialamide-pretreated old rats than in young and mature rats, suggesting that there was a smaller inhibition of the metabolism of dopamine in the limbic forebrain of old rats after nialamide pretreatment. In support of this hypothesis, nialamide (25-100 mg/kg i.p.), which inhibited monoamine oxidase activity in limbic forebrain homogenates of old, mature and young rats, was a less effective inhibitor of this enzyme in the old rats. These results suggest that the reduced locomotor activity response of old rats to the intra-accumbens injections of dopamine after nialamide pretreatment may be due to the reduced ability of nialamide to inhibit monoamine oxidase (and dopamine metabolism) in these animals.