Pregabalin and topiramate regulate behavioural and brain gene transcription changes induced by spontaneous cannabinoid withdrawal in mice

Abstract

This study examined the actions of pregabalin and topiramate on behavioural and gene transcription alterations induced by spontaneous cannabinoid withdrawal in mice. Tolerance was induced in mice by administration of CP-55,940 (0.5 mg/kg/12 hours; i.p.; 7 days). Behavioural assessment of spontaneous cannabinoid withdrawal was performed by measuring motor activity, somatic signs and anxiety-like behaviour on days 1 and 3 after cessation of treatment with CP-55,940. On days 1-3 of cannabinoid withdrawal, mice received pregabalin (40 mg/kg/12 hours; p.o.) or topiramate (50 mg/kg/12 hours; p.o.) and their actions on signs of withdrawal and anxiety-like behaviour were evaluated. The administration of CP-55,940 decreased rectal temperature and motor activity on day 1. On day 1 after interruption of cannabinoid administration, motor activity and the number of rearings increased compared with control group. Anxiety-like behaviour induced by cessation of cannabinoid treatment increased significantly on days 1 and 3 of withdrawal. The administration of pregabalin or topiramate blocked the motor signs and reduced significantly anxiety-like behaviour. Cannabinoid withdrawal decreased tyrosine hydroxylase (TH) gene expression in the ventral tegmental area and µ-opioid receptor gene expression in the nucleus accumbens (NAcc) and increased CB1 receptor gene expression in the NAcc. Treatment with topiramate or pregabalin blocked the decrease of TH and the increase of CB1 gene expressions induced by cannabinoid withdrawal. Both drugs failed to alter µ-opioid receptor gene expression. These results suggest that pregabalin and topiramate may result useful for the treatment of anxiety-like behaviour and motor symptoms associated with spontaneous cannabinoid withdrawal.

Exposure to predator odor and resulting anxiety enhances the expression of the α2δ subunit of voltage‐sensitive calcium channels in the amygdala

“…In addition, pregabalin was found to reduce anxiety‐like behavior induced by cannabinoid withdrawal in mice (Aracil‐Fernández et al . ). Of particular relevance to our finding is the evidence that pregabalin was effective in a rat model of post‐traumatic stress disorder induced by a 10‐min exposure to predator urine scent (well‐soiled cat litter for 10 min).…”

Pregabalin‐ and topiramate‐mediated regulation of cognitive and motor impulsivity in DBA/2 mice

“…Data shown in Figure 1 clearly indicate that pregabalin presents a potent anxiolytic effect, increasing the time spent in the lighted and open side at all doses tested, supporting the previous hypothesis. Indeed, recent data from a study by our group demonstrated that pregabalin reduces the increase in the anxiety level produced by spontaneous cannabinoid withdrawal in mice (Aracil‐Fernandez et al ., 2011).…”

Novel behavioral assays of spontaneous and precipitated THC withdrawal in mice

“…For example the synthetic cannabinoid, WIN55,212–2 induced wet dog shakes and facial rubs in male rats (Aceto et al, 2001). Similarly, repeated CP55,940 administration induces somatic withdrawal signs and increases plasma corticosterone (Oliva et al, 2004, 2003), and also reduces time in the dark side of the light/dark box in male mice (Aracil-Fernández et al, 2011). In adolescent rats exposed to repeated THC, males spent more time in the open arms of the elevated plus maze and females spent more time in the closed arms during abstinence following repeated THC exposure (Harte-Hargrove and Dow-Edwards, 2012).…”