Poster Title

Effects of Nafadotride on Cocaine-Induced Behavioral Sensitization

Institution

Morehead State University

Abstract

It has recently been suggested that the development of behavioral sensitization to psychostimulant drugs may be related to the development of tolerance in dopamine D3 receptors, which are inhibitory with respect to locomotor behavior (Richtand et al., Neurosci. Biobehav. Rev., 2001). Consistent with this view, the preferential D3 antagonist nafadotride blocks the development of locomotor sensitization to amphetamine (Richtand et al. Brain Res, 2000), and concurrent treatment with the D3 agonist 7-OH-DPAT enhances the development of locomotor sensitization to cocaine (Mattingly et al., Pharmacol. Biochem. Behav., 2001). The purpose of the present study was to determine whether concurrent treatment with nafadotride and cocaine would block the development of sensitization to cocaine. Consequently, groups (n = 7-8 each) of male Wistar rats (250-300g) were first habituated to activity chambers (Med-Associates) and then assigned to four drug treatment groups: vehicle (saline), cocaine (15 mg/kg), nafadotride (0.1 mg/kg, P. Sokoloff, INSERM,Paris, FR), or nafadotride-cocaine. These groups were then tested for activity daily for four days after injections (IP) of the assigned drug(s). All rats were then tested after vehicle injections for two days followed by a cocaine challenge test on the third day after drug treatment. In contrast with previous findings with amphetamine, the results indicated that concurrent treatments with nafadotride did not block the development of locomotor sensitization to cocaine as measured during the pretreatment phase or on the cocaine challenge test. These findings suggest that the development of behavioral sensitization to cocaine is not mediated by the development of tolerance in dopamine D3 receptors.

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Effects of Nafadotride on Cocaine-Induced Behavioral Sensitization

It has recently been suggested that the development of behavioral sensitization to psychostimulant drugs may be related to the development of tolerance in dopamine D3 receptors, which are inhibitory with respect to locomotor behavior (Richtand et al., Neurosci. Biobehav. Rev., 2001). Consistent with this view, the preferential D3 antagonist nafadotride blocks the development of locomotor sensitization to amphetamine (Richtand et al. Brain Res, 2000), and concurrent treatment with the D3 agonist 7-OH-DPAT enhances the development of locomotor sensitization to cocaine (Mattingly et al., Pharmacol. Biochem. Behav., 2001). The purpose of the present study was to determine whether concurrent treatment with nafadotride and cocaine would block the development of sensitization to cocaine. Consequently, groups (n = 7-8 each) of male Wistar rats (250-300g) were first habituated to activity chambers (Med-Associates) and then assigned to four drug treatment groups: vehicle (saline), cocaine (15 mg/kg), nafadotride (0.1 mg/kg, P. Sokoloff, INSERM,Paris, FR), or nafadotride-cocaine. These groups were then tested for activity daily for four days after injections (IP) of the assigned drug(s). All rats were then tested after vehicle injections for two days followed by a cocaine challenge test on the third day after drug treatment. In contrast with previous findings with amphetamine, the results indicated that concurrent treatments with nafadotride did not block the development of locomotor sensitization to cocaine as measured during the pretreatment phase or on the cocaine challenge test. These findings suggest that the development of behavioral sensitization to cocaine is not mediated by the development of tolerance in dopamine D3 receptors.