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Animals with a schizophrenia-like phenotype are differentially sensitive to the motivational effects of cannabinoid agonists in conditioned place preference

Behavioural Brain Research
Publication Date
DOI: 10.1016/j.bbr.2014.04.020
  • Amphetamine
  • Cannabinoid
  • Conditioned Place Preference
  • Neonatal Ventral Hippocampus Lesion
  • Schizophrenia
  • Medicine


Abstract Cannabis is the most consumed illicit drug worldwide, but among patients with a diagnosis of schizophrenia, this consumption is higher suggesting that they are differentially sensitive to cannabis. We chose to study this problematic using a neurodevelopmental model of schizophrenia: neonatal ventral hippocampus lesions (NVHL). In a first study, we compared the locomotor response to novelty, a mild stress and two doses of amphetamine (0.75 and 1.5mg/kg) in sham and NVHL rats at post-natal day 35 (PD35) or 56 (PD56). In a second study, we investigated the valence of the motivational effect of Delta-9-tetrahydrocannabinnol (THC, 0.5mg/kg, i.p.) and the cannabinoid receptor agonist, WIN55,212-2 (WIN, 1mg/kg, i.p.), using the conditioned place preference paradigm; we used a biased procedure that comprised 12 days of testing with 3 paired-conditioning. The effects of this dose of WIN were also measured on locomotor activity. Results confirmed that the adult NVHL animals displayed a stronger locomotor response to the two doses of amphetamine, but not to novelty and a mild stress. In adult NVHL, but not sham animals, WIN stimulated locomotor activity and produced a conditioned place aversion. At the dose tested, THC tended to produce an aversion in adult sham but not NVHL animals. Taken together these findings show that adult animals with a schizophrenia-like phenotype are differentially sensitive to the motivational effect of cannabinoids.

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