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Maternal ethanol consumption produces a reduction in postnatal growth. We have studied especially changes of liver and brain. This reduction is more marked if the alcoholic offspring are maintained with their biological mothers than if they are kept with surrogate mothers. Rats exposed prenatally to alcohol show a marked accumulation of fat in the liver and a significant proliferation of liver endoplasmic reticulum. No change in the postnatal development of liver alcohol (ADH) and acetaldehyde dehydrogenases (ALDH) (high and low Km) is observed in offspring from alcoholic mothers, with the exception of slightly higher ALDH (low Km) for the offspring that remain with alcoholic mothers. The postnatal development of the liver (Na+-K+) ATPase is also similar in control and alcoholic groups. However, in the case of the enzyme from the brain, a lower ATPase activity is observed in the group derived from alcoholic mothers. Interestingly, at 20 days of postnatal period, an induction of the ATPase (from liver and brain) was observed when the group of offspring from alcoholic mothers were kept on an alcohol diet.

The ability of drugs of abuse to increase mesolimbic levels of dopamine is a characteristic associated with their rewarding effects. Exactly how these effects are produced by different substances is not as well characterised. Our previous work in rats has demonstrated that accumbal glycine receptors (GlyRs) are involved in mediating the dopamine-activating effects of ethanol, and in modulating ethanol intake. In this study the investigation of GlyR involvement was extended to include several different drugs of abuse. By using microdialysis and electrophysiology we compared effects of addictive drugs, with and without the GlyR antagonist strychnine, on dopamine levels and neurotransmission in nucleus accumbens. The dopamine-increasing effect of systemic ethanol and the drug-induced change in neurotransmission in vitro, as measured by microdialysis and field potential recordings, were dependent on GlyRs in nAc. Accumbal GlyRs were also involved in the actions of tetrahydrocannabinol and nicotine, but not in those of cocaine or morphine. These data indicate that accumbal GlyRs play a key role in ethanol-induced dopamine activation and contribute also to that of cannabinoids and nicotine.

Bipolar disorder co-occurs with alcohol use disorder at a rate 3-5 times higher than the general population. We recently reported that individuals with bipolar disorder differ in the positive stimulating and anxiolytic effects of alcohol compared with healthy peers. This study used a randomized, placebo-controlled, cross-over, within-subject alcohol administration design to investigate neurobiological mechanisms within ventral prefrontal cortical (vPFC) systems that may underlie altered sensitivity to alcohol in bipolar disorder (NCT04063384). Forty-seven young adults (n = 23 with bipolar disorder, 64% women) completed clinical assessment and two beverage administration sessions (alcohol and placebo, counter-balanced). Participants were dosed to 0.08 g% breath alcohol concentration during the alcohol condition and completed measures of subjective response to alcohol and an emotional processing fMRI task during the ascending limb. Timing during the placebo condition mirrored the alcohol session. Acute alcohol was associated with reduced functional connectivity between the insula - subcallosal cingulate cortex, and increased connectivity between the left nucleus accumbens - ventromedial PFC in bipolar disorder, but with no change in functional connectivity between these regions in healthy peers. Alcohol-related increases in nucleus accumbens - ventromedial PFC functional connectivity was associated with greater positive stimulating effects of alcohol in bipolar disorder and heavier recent alcohol use. Results suggest vPFC brain systems respond differently to acute alcohol during emotional processing in young adults with bipolar disorder compared with healthy peers, and that vPFC system responses relate to the subjective experience of intoxication and recent alcohol use.

Abstract Ethanol-induced sleep time was measured in mice after administration of L-3,4-dihydroxyphenylalanine (L-DOPA), L-tryptophan (L-TP), DL-5-hydroxytryptophan (5-HTP), serotonin (5HT), DL-5-hydroxyindole-3-acetic acid (5HIAA), and DL-parachlorophenylalanine (pCPA), a serotonin depletor. The pCPA administration, with concomitant reduction of brain serotonin, had no effect on ethanol-induced sleep; TP, 5-HTP and 5HIAA failed also to significantly enhance ethanol sleep in mice. However, serotonin significantly enhanced sleeping time of mice administered an ineffective dose of ethanol. Pretreatment with L-DOPA produced a marked prolongation of ethanol narcosis with a concomitant large increase in whole brain dopamine (DA). Administration of L-DOPA and pCPA, together, produced a smaller augmentation of ethanol effects.

Our presently somewhat limited knowledge of the modulation of the content, release and turnover of endorphins in brain and pituitary by acute and chronic drug treatment is reviewed and discussed particularly in relation to the problem of addiction. In vitro studies in striatal slices and isolated anterior and intermediate/posterior lobes of the pituitary point to the existence of specific interactions between endorphins and neurotransmitters. In vivo studies have revealed acute GABA-mediated effects of benzodiazepines upon striatal levels of met-enkephalin activity. Morphine exerts no acute effects upon endorphin levels, but decreases the levels of particular endorphins in specific areas of brain and pituitary after long-term treatment; somewhat similar effects are observed after prolonged intake of ethanol, whereas chronic haloperidol treatment results in an increase in levels of endorphins in brain and pituitary. Incorporation studies employing the intermediate/posterior lobe of the pituitary have revealed that the changes in beta-endorphin levels produced by prolonged treatment with morphine or haloperidol reflect a respective depressed or enhanced synthesis of the beta-endorphin precursor pro-opiocortin, whilst the enzymatic processing of this precursor remains unmodified. Studies in cell-free preparations demonstrated that m-RNA extracted from the intermediate/posterior lobes of chronically morphinized rats possesses a decreased "activity".

Ethanol (EtOH) exerts deleterious actions on reproductive function at all three levels: the hypothalamus, pituitary, and gonad (HPG). Nitric oxide (NO), a newly identified messenger molecular in a variety of biological systems, has been suggested as playing a role in HPG hormone regulation. NO stimulates luteinizing hormone releasing hormone secretion from the hypothalamus and has variable effects on luteinizing hormone release from the pituitary. NO is inhibitory to testosterone production, and it may also directly inhibit some steroidogenic enzymes. Related studies in the accompanying paper have demonstrated that inhibiting NO synthase (NOS) using various NOS inhibitors can prevent the EtOH‐induced suppression of testosterone on the male HPG axis, and this action is mainly, although not entirely, due to a direct gonadal effect. To further investigate the role of NO in the HPG axis, we assessed the HPG NO‐NOS system by determining NOS mRNA levels, protein levels, and enzyme activity in the presence and absence of EtOH. At the testicular level, EtOH's action did not appear to be mediated by increasing NO content. However, EtOH was able to potentiate NO'S suppressive effect on the testicular synthesis system. One locus where EtOH and NO interacted was at the steroidogenic enzyme level. NQ‐nitro‐l‐arginine methyl ester, a NOS inhibitor, was found to antagonize the EtOH‐induced fall on P‐450 17α‐hydroxylase/C17‐20 lyase mRNA levels when administered along with EtOH. EtOH had no apparent effect on the pituitary NO‐NOS system and its effects on the hypothalamic NO‐NOS system do not explain its ability to reduce luteinizing hormone releasing hormone secretion.

Acute ethanol exposure (8-570 mM) induced potent contractile responses of rings in both basilar and middle cerebral arteries, from dogs, sheep, piglets and baboons, in a dose-dependent manner. The contractions were reproducible and not tachyphylactic. The middle cerebral arteries were found to be more sensitive to ethanol than the basilar arteries. No known pharmacological antagonist, tested, exerted any effects on ethanol-induced contractions. No differences in responsiveness to ethanol in canine cerebral arteries were found between male and female animals or between the presence and the absence of endothelial cells. Removal of extracellular Ca2+ ([Ca2+]o) partially attenuated ethanol-induced contractions, while withdrawal of extracellular Mg2+ ([Mg2+]o) potentiated such contractions. In the complete absence of [Ca2+]o, caffeine and ethanol induced similar, transient contractions followed by relaxation in K(+)-depolarized cerebral vascular tissue. Ethanol-induced contractions were completely abolished by pretreatment of tissues with caffeine. Our results suggest that: (a) acute ethanol intoxication can induce direct contractions (independent of amine, prostanoid or opioid mediation) of diverse mammalian cerebral vascular tissues, including those from primates; (b) these contractile responses are heterogeneous along the cerebrovascular tree and independent of endothelial cells; (c) in addition to a need for [Ca2+]o, an intracellular release of Ca2+ is needed for ethanol to induce contractions; and (d) hypomagnesemia or Mg deficiency potentiates the contractile effects of ethanol on brain vessels and may be a risk factor for ethanol-related, ischemic stroke events.

Male rats were intubated with either 3, 2, or 0 g/kg alcohol, twice daily, for 7 months and were then bred to untreated females. At 18 and 58–62 days of age, male offspring were tested for passive avoidance learning. At 82–88 days of age, another group of male offspring were tested for open field activity after receiving 0, 0.1, or 0.4 mg/kg physostigmine, a cholinesterase inhibitor. Offspring sired by alcohol‐treated fathers required more trials to reach criterion in the passive avoidance task at 18 days of age, but did not differ significantly at 58–62 days of age. These offspring were more active in the open field compared with controls after receiving vehicle, but did not differ from controls after receiving physostigmine. These results suggest animals sired by alcohol‐treated fathers are more active than controls, and this effect is cholingergically mediated. These results are of interest because of their possible relevance to the hyperactivity noted in children born to alcoholic fathers.

Relatively few investigators have made use of the golden hamster as an experimental animal for ethanol studies. This is somewhat surprising insofar as hamsters show a marked preference for ethanol solutions in free-choice experiments. Given a choice of water or a 10% ethanol solution, hamsters will drink 88% of their total fluid as ethanol solution (Arvola and Forsander, 1961). Furthermore, the most preferred concentration of ethanol for the male hamster is 15% (Arvola and Forsander, 1963) in contrast to the rat that shows a preference only for much lower ethanol concentrations.