Endogenous cannabinoids in amygdala and hippocampus in post-mortem brains of Cloninger type 1 and 2 alcoholics

Abstract

Accumulating evidence continues to link certain aspects of the endogenous cannabinoid (EC) system with alcohol dependence, negative reinforcement learning and the modulation of stress response.Specific alterations in brain regions that are related to stress and negative reinforcement learning have been reported to exist in Cloninger type 1 and 2 alcoholics. To study possible differences in profiles of ECs between Cloninger type 1 (n=9), type 2 (n=8) alcoholics and non-alcoholic control subjects (n=10), we analyzed post-mortem amygdala and hippocampus brain samples for several ECs by quantitative liquid chromatography with triple quadrupole mass spectrometric detection. A significant difference was found between these three groups in terms of EC profiles in the amygdala (p = 0.037).In particular, this difference was prominent for variations in docosahexaenoylethanolamine levels, which were significantly higher in type 1 alcoholics (p = 0.022) when compared to controls. There was also a large negative correlation between anandamide concentration and mGlu1/5 receptor density in the hippocampus of Cloninger type 1 alcoholics (R=-0.88, p=0.002), which was not seen in type 2 alcoholics or in controls. Although preliminary, and from relatively small diagnostic groups, these results suggest that the EC profile may be altered in the hippocampus and amygdala of type 1 alcoholics.

Increased steroid hormone dehydroepiandrosterone and pregnenolone levels in post-mortem brain samples of alcoholics

“…2). Correlations between the steroid levels and previous reports of NR2B, GABA-A receptor binding values, and endocannabinoid levels (Kärkkäinen et al, 2013;Kupila et al, 2015;Laukkanen et al, 2013Laukkanen et al, , 2015Lehtonen et al, 2010) were not significant in other brain regions measured (data not shown).…”

“…In the present study, alcoholics were divided into two subgroups according to Cloninger's typology of alcoholism, where antisocial behavior is associated with earlyonset Cloninger type 2 alcoholism, but not with the late-onset type 1 alcoholism (Cloninger, 1995). In these same study subjects, we have previously reported on differences in neurotransmitter systems associated with steroid function, including GABA-A (Laukkanen et al, 2013), NMDA receptor subunit 2B (Kupila et al, 2015), MOR binding (Laukkanen, Kärkkäinen, Kautiainen, Tiihonen, & Storvik, 2015), and brain tissue levels of endocannabinoids (Kärkkäinen et al, 2013;Lehtonen et al, 2010). The secondary aim of the present study was to calculate whether these previously published measurements are correlated with brain steroid levels.…”

“…Measured values, without normalization, were used to evaluate statistical significance in the individual brain regions. Spearman's method was used to calculate correlations between measured steroid concentrations and AGE, BAC, and PMI, as well as previous reports of receptor binding values and endocannabinoid levels (Kärkkäinen et al, 2013;Kupila et al, 2015;Laukkanen et al, 2013Laukkanen et al, , 2015Lehtonen et al, 2010). Cohen's methods were used to calculate effect sizes (d for comparison of two groups and f for comparison of three groups).…”

Changes in the metabolic profile of human male postmortem frontal cortex and cerebrospinal fluid samples associated with heavy alcohol use

“…Although this method has shown alterations in brain metabolite levels in individuals with alcohol use disorder, for example, decreased levels of choline containing compounds, the method is limited to only measuring a handful of metabolites and does not give a good picture of whole metabolic profile level changes (for a review, see Meyerhoff 11 ). Similarly, there are reports on changes in many metabolite classes, for example, ethanolamines, steroids, and neurotransmitters, in human postmortem brains measured with targeted methods 12–14 …”

Altered CB1 receptor coupling to G-proteins in the post-mortem caudate nucleus and cerebellum of alcoholic subjects

“…Similarly, a [ 35 S]GTPγS binding autoradiographic study revealed no changes in the CB 1 receptor functionality in the CA2 field of the hippocampus between alcohol-preferring and non-preferring rats, although there was a decrease in the CA1 and CA3 fields (Ortiz et al, 2004b). Furthermore, it has been also reported that there were no significant differences in hippocampal endocannabinoid levels in post-mortem brains of Cloninger type 1 and 2 alcoholics when compared with C subjects (Kärkäinen et al, 2013).…”