Title:A New Look at an Old Drug: Cumulative Effects of Low Ribavirin Doses in Amphetamine-Sensitized Rats
VOLUME: 26 ISSUE: 31
Author(s):Branka Petković*, Srđan Kesić, Slavica Ristić, Željko Pavković, Jelena Podgorac, Gordana Stojadinović and Vesna Pešić
Affiliation:Department of Neurophysiology, Institute for Biological Research “Siniša Stanković” - National Institute of Republic of Serbia, University of Belgrade, Belgrade, Department of Neurophysiology, Institute for Biological Research “Siniša Stanković” - National Institute of Republic of Serbia, University of Belgrade, Belgrade, Institute for Research and Development, Galenika a.d., Belgrade, Department of Neurobiology, Institute for Biological Research “Sinisa Stankovic” - National Institute of Republic of Serbia, University of Belgrade, Belgrade, Department of Neurophysiology, Institute for Biological Research “Siniša Stanković” - National Institute of Republic of Serbia, University of Belgrade, Belgrade, Department of Neurophysiology, Institute for Biological Research “Siniša Stanković” - National Institute of Republic of Serbia, University of Belgrade, Belgrade, Department of Neurobiology, Institute for Biological Research “Sinisa Stankovic” - National Institute of Republic of Serbia, University of Belgrade, Belgrade
Keywords:ribavirin, amphetamine, behavioral sensitization, motor activity, environmental novelty, body weight, rats.
Abstract:
Background: Psychotic states related to psychostimulant misuse in patients with hepatitis C virus
infection may complicate acceptance and reaction to antiviral treatment. This observation equally applies to the
widely used ribavirin therapy.
Objective: We examined psychomotor and body weight gain responses to low ribavirin doses after cessation of
intermittent amphetamine treatment in adult rats to assess its role in neurobehavioral outcome during psychostimulant
withdrawal.
Method: The model of amphetamine-induced (1.5 mg/kg/day, i.p., 7 consecutive days) motor sensitization and
affected body weight gain was established in adult male Wistar rats. Then, additional cohort of amphetaminesensitized
rats was subjected to saline (0.9% NaCl; 1 mL/kg/day; i.p.) or ribavirin (10, 20 and 30 mg/kg/day, i.p.)
treatment for 7 consecutive days. Animals’ motor activity in a novel environment was monitored after the 1st and
the 7th saline/ribavirin injection. Body weight gain was calculated as appropriate. Determination and quantification
of ribavirin in the brain tissue were performed also.
Results: The 1st application of ribavirin to amphetamine-sensitized rats affected/decreased their novelty-induced
motor activity only at a dose of 30 mg/kg. After the 7th application, ribavirin 30 mg/kg/day still decreased, while
10 and 20 mg/kg/day increased novelty-induced motor activity. These behavioral effects coincided with the time
required to reach maximum ribavirin concentration in the brain. Body weight gain during withdrawal was not
influenced by any of the doses tested.
Conclusion: Ribavirin displays central effects that in repeated treatment, depending on the applied dose, could
significantly influence psychomotor response but not body weight gain during psychostimulant/amphetamine
withdrawal.
