Influence of drugs acting on nitric oxide-dependent pathways on ethanol tolerance in rats

Abstract

The present results suggest that activation or inhibition of NO-dependent pathways increases or blocks rapid tolerance, respectively. These results give additional support to the hypothesis that brain NO plays a role in the development of tolerance to ethanol, but it remains to be confirmed if the same basic cellular mechanisms are also applicable to tolerance to other behavioural and/or physiological effects of this drug.

Systemic and intra-accumbens microinjections of naltrexone interfere with tolerance to ethanol in rats

“…However, further studies will be needed to consolidate this view. Moreover, several neurotransmitter and receptor systems, such as aminobutyric acid (GABA)-A, GABA-B, serotonin, arginine-vasopressin, acetylcholine and nitric oxide (Kalant 1996;Zaleski et al 2001;Wu et al 1994Wu et al , 1996Wazlawik and Morato 2003), and both transcriptional and post-translational modifications in N-methyl D-aspartate (NMDA) and GABA A receptors may participate in ethanol tolerance (Chandler et al 1998). Therefore, it seems that complex interactions contribute to the development of tolerance to ethanol.…”

Effect of isopregnanolone on rapid tolerance to the anxiolytic effect of ethanol

“…These data corroborate the results obtained in other experiments, in which rapid tolerance to the incoordination and hypothermia caused by ethanol consumption was achieved at certain dose levels. [6][7][35][36][37][38] In addition, studies carried out by Khanna et al revealed that rapid tolerance occurs when ethanol is administered on both test days (intoxicated practice) and also in the dummy test (measurements were not actually recorded until the second day of the protocol), suggesting that the behavioral experience on an inclined plane or on the hypothermia test is not crucial for the development of rapid tolerance to ethanol. 36 Our results are also in accordance with those of that study since our animals were tested in the elevated plus-maze only on the second day.…”

Selective mu- and kappa-opioid receptor antagonists administered into the nucleus accumbens interfere with rapid tolerance to ethanol in rats

“…However, further studies are required to substantiate this speculation. Additionally, other neurotransmitters and receptor systems, such as GABA A and GABA B (Chandler et al 1998;Zaleski et al 2001), serotonin (Wu et al 1994), arginine-vasopressin (Wu et al 1996), nitric oxide (Wazlawik and Morato 2003), cannabinoids (Lemos et al 2007), and glutamate (Wu et al 1993;Chandler et al 1998) influence the expression of tolerance to ethanol. Therefore, it is apparent that complex interactions contribute to this phenomenon.…”

“…Moreover, in the last four decades, several studies have suggested the participation of learning in the onset of tolerance to ethanol (Chen 1968;LeBlanc and Kalant 1975;Holloway et al 1989;Kalant 1998;Larson and Siegel 1998). Practice during the intoxicated state may also facilitate tolerance (Mansfield et al 1983;Vogel-Sprott et al 1984;Mayfield et al 1992;Khanna et al 1996), and drugs that impair learning also block tolerance to ethanol (Wu et al 1993;Zaleski et al 2001;Wazlawik and Morato 2003). It was also shown that the systemic injection of a selective dopamine D 1 receptor antagonist blocked rapid tolerance to ethanol in mice (Batista et al 2005) and that dopamine D 1 receptor activation in the nucleus accumbens triggers a phosphorylation cascade that changes the NMDA receptor from an ethanol-sensitive state to an ethanol-insensitive state, thus facilitating adaptive processes related to tolerance (Maldve et al 2002).…”