Ethanol-dependent Rats Research Articles

Characterization of Susceptibility to Audiogenic Seizures in Ethanol-Dependent Rats after Microinjection of γ-Aminobutyric Acid (GABA) Agonists into the Inferior Colliculus, Substantia Nigra or Medial Septum

Characterization of Susceptibility to Audiogenic Seizures in Ethanol-Dependent Rats after Microinjection of γ-Aminobutyric Acid (GABA) Agonists into the Inferior Colliculus, Substantia Nigra or Medial Septum

Neurotransmitter-receptor binding in various brain regions in ethanol-dependent rats

Since chronic ethanol administration has been demonstrated to induce a number of alterations in neurotransmitter utilization, the possibility was investigated that the receptors, on which these transmitters act, are altered because of a modified synaptic input. Male Sprague-Dawley rats were rendered physically-dependent on ethanol by the oral administration of 9–13 g/kg of ethanol each day over a 4 day period. The binding of radioligands specific for α-adrenergic, β-adrenergic, dopaminergic, serotonergic, muscarinic cholinergic, and GABAergic receptors was assessed at various intervals after withdrawal in several areas of the brain. No alteration in receptor binding was observed at any point under the conditions studied. The data suggest that the signs of an ethanol withdrawal syndrome are not mediated through changes in the ability of neurotransmitters to interact with their receptors.

Modification of the actions of ethanol by centrally active peptides

Ethanol (2.0–5.0 g/kg, IP) caused a dose-related impairment of the aerial righting reflex of mice 60 min after injection. Ethanol (3.5 g/kg, IP) given simultaneously with neurotensin (30 μg, IC), bombesin (30 μg, IC) or β-endorphin (20 μg, IC) caused a greater impairment of the reflex than ethanol alone. Simultaneous treatment with ethanol (4.0 g/kg, IP) and thyrotropin-releasing hormone (TRH, 3.0–30 μg, IC) caused less impairment of this measure than ethanol alone. None of the peptides altered the height of aerial righting when administered alone, or when administered with ethanol no peptide altered blood or brain ethanol content. Unexpectedly, TRH (20 and 40 mg/kg, IP) potentiated the action of ethanol by increasing punished licking in water-deprived rats, rather than antagonizing this acute action of ethanol. Like ethanol (1.0 and 2.0 g/kg, IP), β-endorphin (100 μg, IC) suppressed ethanol-withdrawal tremor and audiogenic-seizure susceptibility in ethanol-dependent rats. β-Endorphin (1 μg) and bombesin (10 and 30 μg, IC) reduced only audiogenic-seizure susceptibility. TRH (10–100 μg, IC, or 1–40 mg/kg, IV) and neurotensin (10–100 μg, IC) had no effect on these ethanol-withdrawal signs. These findings suggest that centrally active peptides may play a role in certain acute and chronic actions of ethanol. Because TRH, neurotensin, bombesin and β-endorphin do not alter all actions of ethanol in the same way, an interaction of ethanol with many functionally independent neuronal circuits is suggested.

Induction of self-maintained intoxication in ethanol-dependent rats

Induction of self-maintained intoxication in ethanol-dependent rats

Effect of ethanol on taurine concentration in the brain.

The taurine concentration in the brain was decreased in ethanol-dependent rats, but returned to normal soon after withdrawal of ethanol. It was not affected by acute ethanol administration.

Alterations in neurotransmitter activity after acute and chronic ethanol treatment: studies of transmitter interactions.

Acute and chronic ethanol treatment has multiple effects on the neurotransmitter systems in the nigrostriatal complex. A single dose of ethanol increases striatal dopamine release at low doses, but depresses it at high doses. In ethanol-dependent rats, dopamine release is accelerated during intoxication, but is reduced during a withdrawal syndrome. Concomitantly, high-affinity choline uptake, an index of cholinergic activity, is elevated at times when dopamine release is depressed. Changes in dopaminergic or cholinergic receptor activity do not induce or result from these effects. Neither has a role for GABA or substance P yet been implicated. The data suggest that interactions between at least two trasmitters in the caudate nucleus may occur after acute and chronic ethanol treatment.

β-Adrenergic receptor density in brains of ethanoldependent rats

β-Adrenergic receptor density in brains of ethanoldependent rats

Ethanol dependence in the rat: Temporal changes in neuroexcitability following withdrawal

Electrodes were chronically implanted in the dorsal hippocampus of rats. Pretreatment levels of neural excitability were assessed by determining the duration of direct hippocampal electrical stimulation sufficient to induce forelimb clonus in each rat. Following baseline measurements the rats were administered an alcohol or sucrose-containing liquid diet and 19--22 days later were withdrawan. Two postwithdrawal stimulation sessions were conducted on each animal. Separate groups of ethanol-dependent and control rats were given primary stimulation sessions at 8 h, 24 h, 72 h, or 1 week postwithdrawal. Secondary stimulation sessions were conducted 1 week or 2 weeks postwithdrawal. The results from the primary stimulations indicated that ethanol-dependent animals exhibited significant neural hyperexcitability for at least 72 h, but not 1 week, postwithdrawal. Results from the secondary stimulations demonstrated the presence of a relative neural hypoexcitability in ethanol-dependent groups as compared to controls. The pattern of results suggests, however, that the observed relative neural hypoexcitability was not the direct result of ethanol withdrawal.

Regional brain acetylcholine levels in rats acutely treated with ethanol or rendered ethanol-dependent

Abstract : A study of brain acetylcholine (ACh) levels was undertaken in an attempt to reconcile discrepancies reported on the effects of ethanol treatment on the cholinergic system. ACh levels were measured in six areas of brains of male Sprague-Dawley rats after a single dose of ethanol or after the induction of ethanol dependence. At various times after treatment the rats were euthanatized by focused microwave irradiation. The excised brains were dissected into the following parts: cerebellum, brain stem, hypothalamus, hippocampus, caudate nucleus and cerebral cortex. After an acute dose of ethanol, ACh levels increased in most areas of the brain when blood ethanol concentrations were quite high. As blood ethanol declined, ACh levels decreased to below control values with similar results observed in ethanol-dependent rats still intoxicated. No significant changes in ACh levels were observed in ethanol-dependent rats undergoing a withdrawal syndrome. These data suggest that ethanol treatment exerts multiple effects on the cholinergic system, but they do not as yet support a role of ACh in the expression of the ethanol withdrawal syndrome. The results of this study provide further information on the development and exploration of models for chronic insults to the brain, such as long-term exposure to toxic chemicals and ionizing and nonionizing radiation. (Author)

BRAIN CONCENTRATIONS OF BIOGENIC AMINE METABOLITES IN ACUTELY TREATED AND ETHANOL‐DEPENDENT RATS

1 Mass fragmentography was used to measure whole brain concentrations of some of the major metabolites of tyramine, octopamine, dopamine and noradrenaline in acutely treated and in ethanol-dependent rats. 2 Treatments with ethanol, either acutely or chronically, failed to alter significantly brain concentration of p-hydroxphenylacetic and p-hydroxymandelic acid (metabolites derived from tyramine and octopamine respectively). The effect on catecholamine metabolites was marked and therefore suggests that ethanol is selective in its effect on central metabolism of biogenic amines. 3 Acute ethanol treatment significantly increased brain concentration of homovanillic acid (HVA), 3,4-dihydroxyphenylacetic acid (DOPAC) and 3-methoxy-4-hydroxyphenylglycol (MHPG). Vanilmandelic acid (VMA) was not affected. All four metabolites (HVA, DOPAC, MHPG and VMA) were increased in the brains of rats rendered dependent on ethanol while still intoxicated (blood ethanol levels above 200 mg/dl). In ethanol-dependent rats undergoing ethanol withdrawal syndrome (no ethanol present in blood), the brain concentrations of HVA and DOPAC were normal while those of MHPG and VMA continued to be elevated. 4 From the decline in the concentrations of HVA and DOPAC after 50 mg pargyline/kg in control rats and rats acutely treated with ethanol, it was concluded that ethanol has no effect on the transport of phenolic acids across the blood brain barrier. 5 No reversal in the metabolism of catecholamines from an oxidative to a reductive pathway, analogous to that produced by ethanol in the periphery, could be established in the brain. 6 The increase in catecholamine metabolite concentrations after ethanol treatment, either acute or chronic, were interpreted as manifestations of increases catecholamine turnover.