A conditioning model of alcohol tolerance.

Tolerance to several effects of ethanol can be learned in a classical conditioning paradigm. In the conditioning model of tolerance, a response compensatory in nature to the effect of ethanol develops in association with the cues that signal the presence of ethanol. Tolerance produced by this procedure (environment-dependent tolerance) differs in several respects from tolerance produced in a paradigm in which learning would not be expected to play a significant role (environment-independent tolerance).

Effects of ethanol on calmodulin levels in mouse striatum and cerebral cortex.

Chronic ethanol administration has previously been shown to produce alterations in cAMP metabolism in neural tissue. The current study investigated the role of calmodulin (CM) in mediating these effects of ethanol. The levels and subcellular distribution of CM in mouse cerebral cortex were not altered at 0, 8 or 24 hr following withdrawal of mice from chronic ethanol administration.

Effect of ethanol on synaptosomal sialic acid metabolism in the developing rat brain.

The total, glycoprotein-bound and glycolipid-bound sialic acid concentration, ad the activities of ecto-sialyltransferase and neuraminidase were determined in synaptosomes from preweanling ethanol-treated and control rats. The period of treatment corresponded to that of maximal synaptogenesis and peak synthesis of sialoglycocompounds (days 27-37 postconception). The average of the peak blood ethanol concentration was 271 mg/100 ml.

Vasopressin maintenance of ethanol tolerance requires intact brain noradrenergic systems.

We have demonstrated that the mammalian antidiuretic hormone, arginine vasopressin (AVP), will maintain functional tolerance to the hypnotic effect of ethanol in mice, beyond the time in which such tolerance normally dissipates. However, when mice are made tolerant to ethanol and then injected intraventricularly with 6-hydroxydopamine (6-OHDA), AVP is no longer effective in maintaining tolerance. The action of AVP was attenuated by a dose of 6-OHDA which significantly lowered brain norepinephrine, but not dopamine levels, suggesting that the maintenance of ethanol tolerance by AVP may require the presence of intact noradrenergic pathways in brain.

Prenatal phenobarbital treatment and temperature-controlling dopamine receptors.

Pregnant mice were fed a phenobarbital-containing diet on days nine through 18 of pregnancy. Following parturition, the offspring of such animals were allowed to reach adulthood and then were tested for their response to an acute injection of apomorphine. Male offspring were less sensitive, while female offspring were more sensitive than matched controls to apomorphine-induced hypothermia.

Alcohol interactions with brain opiate receptors.

Ethanol, added in vitro to mouse caudate membranes, inhibited high-affinity binding of 0.2 nM 3H-dihydromorphine (3H-DHM) over an ethanol concentration range of 250-1,000 mM. At lower, physiologically-attainable ethanol concentrations (e.

Neurochemical correlates of tolerance and strain differences in the neurochemical effects of ethanol.

The behavioral and neurochemical effects of acute and chronic ethanol administration were studied in BALB/c, C57B1/6 and DBA/2 mice. The rates of dopamine synthesis and release in the striatum were estimated by measuring the accumulation of DOPA and DOPAC, respectively, after inhibition of aromatic amino acid decarboxylase with NSD-1024. Biphasic behavioral effects were found in BALB/c and DBA/2 mice, but not in C57B1/6 mice, with low doses of ethanol producing activation and high doses, depression.

Acute alcohol intoxication, mood states and alcohol metabolism in women and men.

The course of alcohol absorption and elimination was investigated in seven women and nine men administered a moderate (0.66 ml/kg) dose of 95% ethanol. Women were tested during the postmenstrual phase (Day 6-7), when levels of estrogen and progesterone were estimated to be relatively low.

Antagonism of the behavioral effects of ethanol by naltrexone in BALB/c, C57BL/6, and DBA/2 mice.

The effects of naltrexone on the increase in locomotor activity induced by a low dose (1.35 g/kg IP) of ethanol and on the duration of loss of righting reflex after a high dose (3.5 g/kg) of ethanol were studied in BALB/c, DBA/2, and C57BL/6 mice.

Ethanol effects on striatal dopamine receptor-coupled adenylate cyclase and on striatal opiate receptors.

The perturbation of neuronal cell membranes by ethanol may result in specific functional changes through modification of the activity of various membrane-bound proteins. In mouse striatum, adenylate cyclase, a membrane-bound enzyme, is coupled to dopamine, as well as to opiate, receptors. Ethanol stimulates striatal adenylate cyclase activity by modifying the regulatory protein ("G-protein")-adenylate cyclase interaction to produce an increased amount of activated enzyme.

On the mechanism by which dopamine inhibits prolactin release in the anterior pituitary.

An in vitro perfusion system was used to assess the effects of chloride channel blockers, dopamine (DA) receptor agonists and antagonists, and GABA receptor agonists and antagonists on prolactin release from the mouse anterior pituitary. Dopamine and muscimol inhibited prolactin release (IC50 = 6 X 10(-8)M and 10(-5)M respectively). The GABA receptor antagonist bicuculline blocked the inhibition of prolactin release by muscimol but not dopamine.

Does tolerance develop to the activating, as well as the depressant, effects of ethanol?

Genetically determined differences were demonstrated in the response of mice to low doses of ethanol. Ethanol (1.35 g/kg) produced an increase in locomotion in DBA/2 and BALB/c mice, but did not alter the locomotor activity of C57B1/6 mice.

Effects of ethanol on Arrhenius parameters and activity of mouse striatal adenylate cyclase.

Arrhenius plots of basal and dopamine (DA)-stimulated adenylate cyclase activities exhibited discontinuities at 20 degrees, while the plot of fluoride-stimulated adenylate cyclase activity was linear over the studied temperature range. None of the Arrhenius parameters were altered by in vitro addition of ethanol (75 or 750 mM) to enzyme assay mixtures, and Arrhenius parameters were found to be unchanged when enzyme obtained from animals rendered tolerant to, and physically dependent on, ethanol was assayed. The differences between the response to ethanol of adenylate cyclase and the response of other membrane-bound enzymes [e.

Effects of the convulsant methionine sulfoximine on striatal dopamine metabolism.

Experiments were conducted to investigate the effects of the convulsant L-methionine-DL-sulfoximine (MSO) on striatal dopamine (DA) metabolism. Intraventricular injections of MSO produced a transient increase in striatal DA release followed by inhibition of DA release for up to 3 days, which paralleled the inhibition by MSO of the enzyme glutamine synthetase (GS). DA synthesis was decreased for up to 24 h after injection of MSO, but returned to normal within 3 days after MSO administration.

Alterations in opiate receptor function after chronic ethanol exposure.

The dose-response curve for morphine-induced stimulation of striatal dopamine metabolism was shifted to the right in mice which had been withdrawn for 24 hours after chronic consumption of an ethanol-containing liquid diet. The apparent ED50 for morphine was increased by 33% in ethanol-treated mice. Concomitant with the shift in the dose-response curve, the affinity for dihydromorphine of the high-affinity caudate morphine receptor was decreased in ethanol-treated mice.

Modification of environmentally cued tolerance to ethanol in mice.

Tolerance to the hypnotic and hypothermic effects of ethanol in mice develops with multiple injections. The tolerance to both of these effects of ethanol can be reduced by testing the animals in a novel environment, suggesting that the tolerance may be learned. Tolerance to the hypothermic effect of ethanol develops more rapidly than tolerance to the hypnotic effect.

Ethanol alters kinetic characteristics and function of striatal morphine receptors.

Morphine was shown to promote dopamine (DA) synthesis and release in mouse striatum, but mice rendered tolerant and dependent on ethanol were found to be less responsive to morphine's effects on striatal DA metabolism than control animals. Ethanol feeding also produced a change in the affinity of striatal "opiate" receptors for [3H]dihydromorphine, and these ethanol-induced receptor changes may be responsible for the altered biological effect of morphine.

Audiogenic seizures and neuronal deficits following early exposure to barbiturate.

Sabra mice (n = 232) received phenobarbital (PhB) during the period of their prenatal development (PB group), or during the period of their neonatal development (NB group). PB mice received the barbiturate transplacentally by feeding their mothers PhB in their diet (3 g/kg food) on gestation days 9-18. NB mice received daily injections of PhB on postnatal days 2-21.

Centrally acting peptides and tolerance to ethanol.

Among the many factors that may influence the development or expression of functional tolerance to or physical dependence on ethanol is the neurohypophyseal hormone, arginine vasopressin (AVP). This peptide hormone, administered exogenously, maintains ethanol tolerance in animals once such tolerance has been established. An analog of the hormone has also been reported to facilitate the development of ethanol tolerance and to exacerbate ethanol withdrawal symptomatology.

Receptor-mediated dopaminergic function after ethanol withdrawal.

Striatal dopamine (DA) synthesis, measured in vivo as accumulation of DOPA after aromatic amino acid decarboxylase inhibition, is increased by neuroleptics and decreased by DA agonists as a result of their interactions with regulatory receptors. A sensitive high performance liquid chromatography (HPLC) technique has been developed, which allows the evaluation of both increases and decreases in DOPA levels in response to agonists and antagonists, and simultaneously permits measurement of DA levels as an indication of DA neuronal activity. C57BL mice, after chronic ethanol treatment and withdrawal, demonstrate significantly decreased responses, in terms of DOPA accumulation and DA release, to both haloperidol, a DA antagonist, and apomorphine, a DA agonist.