Brain and Plasma Tetrahydroisoquinolines in Rats: Effects of Chronic Ethanol Intake and Diet

Abstract

Brain concentrations of salsolinol (SAL), a simple tetrahydroisoquinoline (sTIQ) condensation product of dopamine (DA) and acetaldehyde, are reported to increase in chow-fed rats drinking ethanol/H2O ad libitum. However, our analyses showed that rat chow contains traces of SAL and, as previously reported, appreciable 3,4-dihydroxyphenylalanine (DOPA), a sTIQ precursor. To examine the effect of consumption of ethanol in a DOPA- and SAL-free diet on endogenous sTIQs, we analyzed two brain regions and blood plasma of rats undergoing prolonged intake (3 weeks and 23 weeks) of liquid diet containing 6.6% ethanol or isocaloric carbohydrate. SAL and three other DA-related sTIQs were quantitated using capillary gas chromatography/mass spectrometry in the selected ion mode with deuterated standards. In accord with studies on ethanol/chow-fed rats, sTIQ concentrations in hypothalamus were elevated after 3 weeks of ethanol, although after 23 weeks, hypothalamic sTIQs were either unchanged or reduced (O-methylated SAL). Furthermore, sTIQ concentrations in corpus striatum and, with one exception, plasma were not altered by ethanol ingestion for either duration. (However, 23 weeks of ethanol intake significantly reduced the striatal concentrations of DA and its acid metabolite, presumably reflecting neurotoxicity.) Reasoning that DOPA in diet might underlie the reported ethanol-dependent increases in striatal sTIQs, we found that L-DOPA supplementation (500 micrograms/rat/day) of EtOH/liquid diet-fed rats for 13 weeks tended to increase striatal SAL. Overall, the data indicate that elevations in endogenous sTIQ concentrations due to prolonged ethanol intake depend on the brain region, duration of intake, and even associated dietary constituents. In that regard, the higher striatal SAL concentrations in rats drinking ethanol ad libitum could have been facilitated by DOPA and perhaps SAL consumed in lab chow.

A Critical Evaluation of Influence of Ethanol and Diet on Salsolinol Enantiomers in Humans and Rats

“…Chronic ethanol treatment has been reported to have no effect on SAL levels in rat hypothalamus or striatum (Collins et al, 1990; Haber et al, 1999; Myers et al, 1985b), whereas others reported that the SAL levels increased in the various rat brain regions (Haber et al, 1999; Matsubara et al, 1987; Myers et al, 1985a; Sjöquist et al, 1982; Starkey et al, 2006). Recently, Rojkovicova and colleagues (2008) also reported that SAL levels increased and R/S ratio decreased in both putamen and midbrain regions of P rats following alcohol consumption, suggesting an increase in the ethanol-induced nonenzymatic production of SAL.…”

“…Despite the extensive studies, the influence of acute or chronic ethanol on SAL levels in humans as well as in experimental animals has been controversial (Adachi et al, 1986; Collins et al, 1979, 1990; Faraj et al, 1989; Feest et al, 1991; Musshoff et al, 1997, 2005; Rommelspacher et al, 1995; Sjöquist et al, 1982, 1985). The present study demonstrated that ethanol infusion did not increase plasma SAL levels in healthy subjects (Fig.…”

Mystic Acetaldehyde: The Never-Ending Story on Alcoholism

“…Moreover, the investigations reporting increased brain salsolinol upon chronic ethanol intake or chronic ethanol administration, were performed in rats allowed to access ad libitum lab chow either before and throughout the study (Sjöquist et al, 1982). Interestingly, when such rat studies were repeated using chronic ethanol intake in DOPA- and salsolinol-free liquid diets, no changes were found of endogenous brain salsolinol concentrations (Collins et al, 1990). However, when the ethanol-liquid diets were supplemented with DOPA, salsolinol levels were raised (Collins et al, 1990) suggesting that, upon prolonged ethanol intake, elevations of endogenous salsolinol concentrations, as well as of those of other THIQs, seem to depend on a number of factors including the brain region investigated, the duration of intake and the associated dietary constituents (Lee et al, 2010).…”

“…Interestingly, when such rat studies were repeated using chronic ethanol intake in DOPA- and salsolinol-free liquid diets, no changes were found of endogenous brain salsolinol concentrations (Collins et al, 1990). However, when the ethanol-liquid diets were supplemented with DOPA, salsolinol levels were raised (Collins et al, 1990) suggesting that, upon prolonged ethanol intake, elevations of endogenous salsolinol concentrations, as well as of those of other THIQs, seem to depend on a number of factors including the brain region investigated, the duration of intake and the associated dietary constituents (Lee et al, 2010). The differences observed in the data from these studies have been extensively summarized and analyzed in a previous review on this specific topic (Hipólito et al, 2012).…”

Acetaldehyde production capacity of salivary microflora in alcoholics during early recovery

“…A recent study by Clarke, Adermark, Chau, Söderpalm, and Ericson (2014), however, showed that alcohol itself causes the increase in dopamine neurotransmission and not acetaldehyde. Still, acetaldehyde influences dopaminergic neurotransmission and thus reward function by diverting dopamine breakdown to form tetrahydroisoquinolines (Collins, Ung-Chhun, Cheng, & Pronger, 1990;Davis & Walsh, 1970;Duncan & Deitrich, 1980;Myers, 1989;Myers et al, 1985). These opioid agonists are substitutes for enkephalins and play an important part in mediating the effect of alcohol on the reward area (Lucchi, Bosio, Spano, & Trabucchi, 1982;Melis, Carboni, Caboni, & Acquas, 2015).…”