Hyperactivity induced by dexamphetamine/chlordiazepoxide mixtures in rats and its attenuation by lithium pretreatment: a role for dopamine?

Abstract

Dexamphetamine (DEX) and chlordiazepoxide (CDZP) given together as mixtures have previously been shown to induce a characteristic "compulsive" form of locomotor hyperactivity in rats placed in unfamiliar environments, which was much greater than activity obtained with any dose of either drug given separately; acute pretreatment with lithium counteracted mixture-induced hyperactivity. The role of dopamine in these effects was investigated by measuring concurrently the levels of dopamine (DA), dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the striatum. DEX (0.02-2 mg kg-1) increased horizontal (entries) and vertical (rears) activity, and increased DA and decreased DOPAC and HVA in the striatum. Chlordiazepoxide (CDZP) (12.5 or 20 mg kg-1) increased horizontal activity but did not affect vertical activity or DA or its metabolites. Lithium by itself in acute (2 meq kg-1, 24 and 4 h before test) or extended (2 meq kg-1 daily for 9 days) dosage had little effect on horizontal or vertical activity or levels of DA or DOPAC. Given together, DEX and CDZP (1.18 mg kg-1 + 12.5 mg kg-1), as expected, increased entries much more than did either drug given separately, but rears and levels of DA and metabolites remained similar to those with DEX given alone. Acute lithium pretreatment counteracted the mixture-induced increase in entries. Neither acute nor extended lithium pretreatment significantly altered DEX-induced changes in activity or levels of DA or DOPAC.(ABSTRACT TRUNCATED AT 250 WORDS)