Abstract:
:Both natural and synthetic cannabinoid receptor (e.g., CB1) agonists such as Δ(9)-THC, WIN 55,212-2 (WIN-2), and HU-210 disrupt spatial cognition presumably through the inhibition of synchrony of hippocampal ensemble firing to task-related events. Although the CB1 receptor agonist CP 55,940 also disrupts the synchronous firing of hippocampal neurons, it does not seem to affect the average firing rate. This difference is not readily explained by the chemical structure and pharmacology of the different compounds thus warranting a more detailed examination into (i) how other cannabinoids affect the spontaneous firing, bursting, and cell synchrony of hippocampal principal cells located in CA3 and CA1 subfields, and (ii) whether these effects are indeed mediated through CB1 receptors, which will be explored by the selective antagonist AM-251. Male Long-Evans rats surgically implanted with multielectrode arrays to hippocampal CA3 and CA1 were anesthetized and principal cells discharging at 0.25-6.0 Hz were isolated and "tracked" following the systemic administration of Tween-80, Δ(9)-THC (1 or 3 mg/kg) or WIN-2 (1 mg/kg) or HU-210 (100 μg/kg), and 1.5 mg/kg AM-281. All cannabinoids except for 1 mg/kg Δ(9) -THC reliably reduced average firing rates and altered "burst" characteristics, which were reversible with AM-281 for Δ(9)-THC and WIN-2 but not for HU-210. In addition, all cannabinoids disrupted intrasubfield and intersubfield ensemble synchrony of pyramidal cells, which is an effect insensitive to AM-281 and thus unlikely to be CB1 mediated. We consider these cannabinoid effects on spike timing and firing/bursting of principal hippocampal neurons carried by CB1 and non-CB1 receptors to be physiological underpinnings of the cognitive impairments inherent to cannabinoid exposure.
journal_name
Hippocampusjournal_title
Hippocampusauthors
Goonawardena AV,Riedel G,Hampson REdoi
10.1002/hipo.20769subject
Has Abstractpub_date
2011-05-01 00:00:00pages
520-31issue
5eissn
1050-9631issn
1098-1063journal_volume
21pub_type
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