Dose-Dependent Effects of Chronic Amphetamine Administration in Local Cerebral Glucose Utilization in Rat

Abstract

The daily dose of amphetamine pretreatment may affect the development of behavioral-sensitized patterns in rodents and amphetamine psychosis in humans. This experiment investigated the regional cerebral metabolic changes in rats after pretreatment with different doses of amphetamine by the 2-[¹⁴C] deoxyglucose method. Rates of local cerebral glucose utilization were examined in 37 regions of the rat brain. The result showed generally maximal metabolic augmentation in the 5.0 mg/kg group instead of in the 1.0 or the 10.0 mg/kg groups. Behavioral testing using motor activity cages in rats with the same regimen found no difference among groups. The findings demonstrate that there might be a window effect by daily amphetamine dose on the development of drug dependence and amphetamine psychosis. It was suggested that the 2-[¹⁴C]deoxyglucose method could be used for further study of animal models of amphetamine psychosis.

Reduced Regional [¹⁴C]2-Deoxyglucose Uptake in Response to Long-Term Clozapine Administration in Rats

“…The decreased 2-DG uptake after haloperidol administration is thought to result from blockade of dopamine neurotransmission in the striatum [5,10]. This is supported by our previous studies of rats treated with long-term amphetamine, a dopaminergic stimulant [11,12]. In these studies, we found that several regions, especially the dopaminergic system, had elevated 2-DG uptake after long-term amphetamine administration.…”

Amphetamine sensitization: Nonassociative and associative components.

“…The development of sensitization and the testing included 3 stages (Huang et al, 1995(Huang et al, , 1997): In the pretreatment stage, rats were injected intraperitoneally with d-AMPH (1 mg/kg, Sigma Chemical, St. Louis, MO) or saline (control) daily for 2 weeks. Following each injection, rats were placed into one of the three contexts for 120 min before being returned to the home cage.…”

“…This "nonassociative" view, however, fails to explain the result showing a complete lack of behavioral sensitization under some conditions. For example, it has been shown, with 2-deoxyglucose imaging technique, that repeated administrations of AMPH (1 mg/kg) for 14 days, followed by 7 days of abstinence, altered metabolism in many brain areas in response to challenge of AMPH (0.5 mg/kg); however, no behavioral sensitization was observed (Huang et al, 1995(Huang et al, , 1997. This puzzling dissociation between presence of brain change and absence of behavioral expression has now become explainable.…”

Differential Development of the Enhanced Metabolic Response during Amphetamine Sensitization

“…The 2-deoxyglucose method can detect regional cerebral metabolic change [3]. By application of this method in this animal model, elevations of local cerebral glucose utilization in the mesolimbic and the nigrostriatal dopaminergic path ways have been shown [4], However, the paradigm used to administer amphetamine is extremely important for studies of sensitization. Chronic amphetamine adminis tration showed general maximal metabolic augmentation in a 5.0-mg/kg group instead of in 1.0-or 10.0-mg/kg groups [4], The timing for the final challenge is also important.…”

“…By application of this method in this animal model, elevations of local cerebral glucose utilization in the mesolimbic and the nigrostriatal dopaminergic path ways have been shown [4], However, the paradigm used to administer amphetamine is extremely important for studies of sensitization. Chronic amphetamine adminis tration showed general maximal metabolic augmentation in a 5.0-mg/kg group instead of in 1.0-or 10.0-mg/kg groups [4], The timing for the final challenge is also important. The influence of the withdrawal period on the appearance of behavioral sensitization has been noted previously [5], Behavioral sensitization elicited by re peated administration of amphetamines does not fully develop until a period after discontinuation of the am phetamines, but then persists undiminished for a long time [1,[5][6][7],…”