Evidence for a role for dopamine in the diazepam locomotor stimulating effect

Abstract

It is well known that benzodiazepines produce dependence in humans and locomotor stimulation in experimental animals. In this study the possible involvement of catecholamines in the diazepam-induced locomotor stimulation in mice were investigated. Diazepam was found to have a biphasic effect; increasing locomotor activity at a low dose (0.25 mg/kg), while decreasing it at higher doses (greater than 0.5 mg/kg). The locomotor stimulating effect of diazepam was effectively blocked by pretreatment with the benzodiazepine receptor antagonist flumazenil, as well as with the catecholamine synthesis inhibitor alpha-methyltryrosine and the dopamine receptor antagonists haloperidol, spiperone and SCH 23390. Taken together, these data indicate that the locomotor stimulating effect observed after low doses of diazepam is due to activation of brain dopaminergic systems involved in locomotor activity. The observations are discussed in relation to the hypothesis that dependence-producing drugs activate specific brain reward systems.

Behavioral and hormonal responses to stress in the newborn mouse: Effects of maternal deprivation and chlordiazepoxide

“…Our data show that high CDP doses reduce UVZ rate; however, because our experiment expanded the range of doses previously used, we found that at low CDP doses (2 mg/kg) there is a tendency for UVZ rate to increase compared to controls. CDP effects on 8-day-old mouse pups' UVZ resemble previous data showing that behavioral responses to specific GABA-A agonists, such a muscimol, or BDZ agents, such as diazepam and CDP, are biphasic in both adult and developing mice (Gardner & Piper, 1982;Laviola & Alleva, 1990;Sansone, 1979;Soderpalm, Svensson, Hulthe, Johannessen, & Engel, 1991 ;Tirelli, Jodogne, & Perikel, 1991). Furthermore, they confirm the previous finding of an "adultlike" activity of the GABAergic system very early during ontogeny (Tirelli et al, 1991).…”

Comparison of SHR, WKY and Wistar rats in different behavioural animal models: effect of dopamine D1 and alpha2 agonists

“…The same was seen with amphetamine. Both compounds were tested at doses that did not significantly affect locomotion as hyperlocomotion is described to further enhance anxietyrelated parameters and, thus, imply less anxiety (Dawson et al 1995;Soderpalm et al 1991).…”

Characterization in Rats of the Anxiolytic Potential of ELB139 [1-(4-Chlorophenyl)-4-piperidin-1-yl-1,5-dihydro-imidazol-2-on], a New Agonist at the Benzodiazepine Binding Site of the GABAA Receptor

“…Partly, it is associated with an increased exploratory activity due to its anxiolytic effect. However, it is also described as a nonspecific hyperlocomotion, which, because the anxiety-related parameters are influenced by the locomotor activity of the animals, may further enhance these parameters and thus the anxiolytic activity (Soderpalm et al, 1991;Dawson et al, 1995). Additionally, the hyperlocomotion is discussed as a reflection of the psychostimulant effect of diazepam (Ikemoto, 2004).…”