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Effects of acute systemic and intra-cerebral stimulation of cannabinoid receptors on sensorimotor gating, locomotion and spatial memory in rats

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Abstract

Rationale

Cannabinoid CB1 receptors in the brain are targets of both endocannabinoid signalling and the psychoactive compounds of the hemp plant. They mediate neuronal effects of their ligands in various corticolimbic and striatal circuits by presynaptic regulation of transmitter release.

Objectives/Methods

This study investigates acute systemic effects of the full CB1 receptor agonist WIN 55,212-2 (WIN) on prepulse inhibition (PPI) of the acoustic startle response (ASR), locomotor activity and spatial memory retrieval in an eight-arm radial-maze task. Furthermore, we tested the effect of local intra-cerebral micro-infusions of WIN into the nucleus accumbens (NAc), ventral tegmental area (VTA), dorsal (dHIP) and ventral (vHIP) hippocampus and medial prefrontal cortex (mPFC).

Results

Systemic WIN (1.2 mg/kg) reduced PPI without affecting ASR, had no effect on locomotion in the open field, but impaired retrieval of spatial memory. Infusions of 5 μg/0.3 μl WIN into either NAc (core or shell), dHIP or VTA did not affect PPI and locomotion immediately afterwards. However, PPI was significantly reduced after intra-mPFC and intra-vHIP infusion of WIN. Furthermore, WIN infusion into dHIP increased the number of reference memory errors in the maze, suggesting impairment of memory retrieval.

Conclusions

Our data support the notion that CB1 receptor stimulation impairs sensorimotor gating most likely by modulation of neurotransmitter release in mPFC and vHIP. The lack of effects of local WIN infusions in NAc and VTA might be due to low receptor abundance in these regions. Additionally, CB1 receptor activation in dHIP impairs spatial memory retrieval. Taken together, cortico-hippocampal cannabinoid receptors play an essential role in the regulation of cognitive and behavioural processes.

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  1. Brain Research Institute, Department of Neuropharmacology, University of Bremen, P.O. Box 330440, 28334, Bremen, Germany

    Nico Wegener, Sybille Kuhnert, Annika Thüns, Rasmus Roese & Michael Koch

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  1. Nico Wegener
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  2. Sybille Kuhnert
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  4. Rasmus Roese
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  5. Michael Koch
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Correspondence to Nico Wegener.

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Wegener, N., Kuhnert, S., Thüns, A. et al. Effects of acute systemic and intra-cerebral stimulation of cannabinoid receptors on sensorimotor gating, locomotion and spatial memory in rats. Psychopharmacology 198, 375–385 (2008). https://doi.org/10.1007/s00213-008-1148-1

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