Psychomotor activity and body weight gain after exposure to low ribavirin doses in rats: role of treatment duration

Abstract

Clinically-related basic studies on the behavioral effects of ribavirin treatment are still lacking despite its wide use as an antiviral medication. This paper considers the effects of low ribavirin doses (10, 20 and 30 mg/kg/day) on psychomotor activity (novelty-induced exploratory behavior, d-amphetamine (AMPH, 1.5 mg/kg, intraperitoneal)-induced motor activity), and body weight gain in socially undisturbed adult male Wistar rats 24 h after the first, seventh and fourteenth once-a-day injection. Low doses of ribavirin were tested in an attempt to avoid the recognized systemic side effects related to high-dose usage. None of the singly applied ribavirin doses affected exploratory/spontaneous and AMPH-induced motor behavior (locomotion, stereotypy-like and vertical activity), however, body weight gain was significantly lower after treatment with 30 mg/kg of ribavirin. The 7-and 14-day treatments with 10 and 30 mg/kg/day of ribavirin significantly suppressed novelty-induced locomotion and body weight gain; the 14-day treatment with ribavirin at a dose of 30 mg/kg/ day decreased AMPH-induced stereotypy. These findings indicate that repeated application (up to 14 days) of low ribavirin doses results in low novelty-induced locomotion along with reduced weight gain, accentuating the existence of a U-shaped dose-response relationship with a prolonged duration of ribavirin treatment.

A New Look at an Old Drug: Cumulative Effects of Low Ribavirin Doses in Amphetamine-Sensitized Rats

“…Importantly, body weight gain during the withdrawal period was not influenced by ribavirin treatment. In line with our previous findings [20] , these data point to the critical role of the previous drug experience for the behavioral outcome during low-dose ribavirin therapy after cessation of intermittent AMPH usage.…”

“…Results of this study contribute to the view of psychostimulant withdrawal-induced reductions in motivation for a natural reward, such as food (reviewed in [40]). By comparing the influence of 7-day exposure to ribavirin (10, 20 and 30 mg/kg/day; [20]) and AMPH (1.5 mg/kg/day, current study) on body weight gain in drug-naive animals, we obtained a surprising finding about highly similar potency of these two drugs to slow down/diminish body weight gain during the injection period, with the important notion of U-shaped dose-response relationship in ribavirin treatment [20]. Such experimental findings have not been addressed previously, though clinical findings accentuate the relationship between combined interferon (IFN)-ribavirin therapy and decreased appetite/weight loss in patients (e.g., [5,54]), viewing the observed phenomenon as IFN-related without questioning the contribution of ribavirin by itself.…”

“…It seems that in conditions of disturbed central neurotransmission, the primary role of ribavirin could be to maintain a steady state and prevent functional and metabolic activation. Most previous studies have found that A1 agonists, including ribavirin [21], do not significantly affect the release of neurotransmitters or motor activity in basal conditions, but at the same time they show evident attenuating effect when these processes are stimulated [15,16,20,[22][23][24]. Also, microinjection of A1 agonist into the nucleus accumbens was sufficient to reverse the expression of cocaine sensitization in rats [25].…”

“…Peculiarities in dose-related cumulative effects of ribavirin related to acute AMPH exposure have been accentuated in a previous study of our group [20]. However, those effects have never been deliberately examined in subjects/animals that passed repeated intermittent administration of psychostimulant/AMPH, as they already have an affected brain neurochemistry and behavior.…”

“…Ribavirin at low doses has already been proven to be effective in some animal models [15][16][17][18][19][20]. It seems that in conditions of disturbed central neurotransmission, the primary role of ribavirin could be to maintain a steady state and prevent functional and metabolic activation.…”