ReviewFunctions of cannabinoid receptors in the hippocampus
Section snippets
Background to the cannabinoids
Mammalian tissues contain at least two types of cannabinoid receptors, CB1 and CB2, both of which have been cloned (for reviews see Pertwee, 1997, Pertwee and Ross, 2002). CB1 receptors are present in the central nervous system and also in certain peripheral tissues (Pertwee, 1997). Within the brain, the distribution of CB1 receptors is heterogeneous, areas expressing this receptor type in particularly high concentrations include the cerebral cortex, hippocampus, lateral caudate-putamen,
Anatomical localisation of cannabinoid receptors in the hippocampus
The anatomical localisation of CB receptors in the brain has been visualised using in situ hybridisation to detect mRNA, and autoradiographic or immunohistochemical labelling of CB receptors themselves. Since it is thought that CB2 receptors are only present in peripheral tissues (Munro et al., 1993, Pertwee, 1997), these studies have focused on the distribution of CB1 receptors. The use of various antibody labels have consistently found the CB1 receptor immunoreactivity to be localised to the
Effects of cannabinoids on release of neurotransmitters
There is abundant evidence that cannabinoids can inhibit the release of several neurotransmitters throughout the brain (see Schlicker and Kathmann, 2001), but in the hippocampus this has focused on GABA and acetylcholine (ACh). Δ9-THC, CP55940, R-(+)-WIN55,212-2 and anandamide all inhibit release of ACh from the hippocampus in vivo (Carta et al., 1998, Gessa et al., 1997, Gessa et al., 1998) or in vitro (Gifford and Ashby, 1996, Gifford et al., 1997a, Gifford et al., 1999, Gifford et al., 2000
Behavioural function of hippocampal cannabinoid receptors
The hippocampus forms part of the medial temporal lobe, a brain structure strongly implicated in learning and formation of ‘declarative’ (Squire, 1987, Squire, 1992) or ‘episodic’ (Tulving, 1983) memory. It is therefore reasonable to assume that CB1 receptor-mediated effects on electrophysiological and cellular responses also translate into behaviourally relevant events. The corollary is that hippocampal CB1 receptors may participate in mechanisms of encoding, consolidation and/or retrieval in
Future directions
The investigation of the effects of cannabinoids on the hippocampus is at an intriguing stage because there is now real cause for optimism that many of the apparent inconsistencies and contradictions in the literature may soon be explained. Just some of the possible points of clarification that are prompted by this review include the following. It will be important to characterise the receptors mediating the effects of R-(+)-WIN55,212-2 on GTPγS binding and excitatory synaptic transmission in
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2019, Pharmacology Biochemistry and BehaviorCitation Excerpt :THC, the main psychoactive constituent of cannabis, is partial agonist at the cannabinoid receptors 1 (CB1-R), which is densely expressed in the hippocampus and the prefrontal cortex, neuroanatomical structures markedly implicated in cognitive processes such as sustained attention, response inhibition and verbal learning and memory (Bhattacharyya et al., 2012; Kucewicz et al., 2011). Preclinical studies indicate that CB1-R are particularly concentrated on presynaptic cholinergic terminals (Lichtman et al., 2002; Davies et al., 2002), which are involved in long-term potentiation (LTP), widely regarded as a neurophysiological substrate of learning and memory (Salavati et al., 2014; Hoffman et al., 2017). By binding at the presynaptic CB1-R located at the cholinergic nerve terminals, cannabinoids may cause inhibition of acetylcholine release, contributing to acute cognitive deficits (Heishman et al., 1990; Solowij et al., 2011; Solowij et al., 2002).
Adolescent Δ<sup>9</sup>-Tetrahydrocannabinol Exposure and Astrocyte-Specific Genetic Vulnerability Converge on Nuclear Factor-κB–Cyclooxygenase-2 Signaling to Impair Memory in Adulthood
2019, Biological PsychiatryCitation Excerpt :Adolescent, not adult, exposure to Δ9-THC was required for the development of deficient recognition memory in adult mice with expression of aDN-DISC1. These results are consistent with other preclinical reports on effects of adolescent exposure to cannabinoids and resulting cognitive impairments (3,70–72). Lack of effects of Δ9-THC in aDN-DISC1 mice on fear conditioning is in line with the unaltered performance in the Morris water maze (73–75) or aversive memory tasks in mice following adolescent treatment with cannabinoids (2,70,76–78).