Haloperidol administered subchronically reduces the alcohol-deprivation effect in mice.

During the pre-experimental phase, hybrid (CBA x C57BL) male mice having had 16 weeks free access to food, water and flavored 30% alcohol were deprived of alcohol for 3 days. The next day they were given free choice between similarly flavored water and 30% alcohol. The mice were divided into two subgroups having (HD) or lacking (LD) the deprivation-induced elevation in alcohol intake during the first 1.5 h of renewed access compared with their intake during the last 22.5 h of first postdeprivation day. In Experiment 1, alcohol naive, LD, and HD mice received daily injections of haloperidol (Haldol; 1 mg/kg) or vehicle during 14 days of abstinence. The behavior of the mice was evaluated in an exploratory cross-maze and inescapable slip funnel test a day after the 13th injection (before the 14th injection). On the first postinjection day, the mice were again given a free choice between flavored water and alcohol. In Experiment 2, all the mice were administered with vehicle during the first 13 days of abstinence. On 14th day, they received an injection of haloperidol (1 mg/kg) or vehicle and a day later were given choice between flavored water and alcohol. Unlike a single injection, the subchronic administration of haloperidol lowered the alcohol intake by HD mice with a more prominent decrease seen during the first 1.5 h than during the last 22.5 h of first postdeprivation day. The alcohol-deprivation effect in HD mice decreased by 79% after subchronic haloperidol. No significant change in alcohol intake was found in alcohol-naive and LD mice. Water intake did not vary systematically. Among the groups, the effect of subchronic haloperidol on the alcohol-deprivation effect did not parallel changes in most of the measures of exploratory or avoidance behavior. It is proposed that haloperidol administered subchronically may attenuate motivation for alcohol.

Opiate withdrawal intensity correlates with the presence of DSLET high-affinity binding.

The goal of this study was to compare the characteristics of mu- and delta-opioid receptors in the cortex of DBA/2 and C57BL/6 mice, which differ in sensitivity to the long- and short-term effects of morphine. The characteristics of mu-opiate receptors were not different in the cortex of both strains. Both high- and low-affinity binding sites of DSLET, a specific ligand of delta-opiate receptors, were present in the cortex of C57BL/6 mice, whereas the high-affinity binding sites were not found in the cortex of DBA/2 mice. The absence of high-affinity DSLET binding sites, which are similar to the delta 2 type of opioid receptors, may explain the less intensive naloxone-precipitated withdrawal reaction of DBA/2 as compared with C57BL/6 mice.

Ethanol and delta-sleep-inducing peptide: effects on brain monoamines.

The brain content of dopamine (DA) and its metabolites [dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA)] were the same in rats with different immobilization times in forced swimming test, while the serotonin (5-HT) concentration was higher in high active (HA, immobilization < 2 min) than low active (LA, immobilization > 5 min) animals. Ethanol (2 g/kg, PO) tended to increase the DA level in the striatum and nucleus accumbens in LA rats and decrease the 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) concentration in HA rats. delta-Sleep-inducing peptide (DSIP) injection reduced the level of 5-HT in the medial prefrontal cortex (MFC) in both groups, did not affect the concentration of DA or DOPAC, but increased HVA in the striatum of HA rats. DSIP injected before ethanol administration augmented the ethanol effects on 5-HT in the MFC and attenuated the action of ethanol on 5-HIAA in the nucleus accumbens. A relationship between the different levels of voluntary alcohol consumption and sensitivity to stress among LA and HA rats and the differences in DA and 5-HT concentrations is suggested. The use of LA and HA rats in developing models for testing of stress-shielding compounds is also described.

Inducing effect of cortisone and insulin on the activity of beta-galactosidase in the E. coli strains K12.

Individual and combined effects of cortisone and insulin on the synthesis of beta-galactosidase in the strains E. coli K 12 200 PS/Flac and M-308 and the possiblity of cortisone uptake by the bacterial cell under different temperature conditions were investigated in their dynamics. When insulin and cortisone are applied simultaneously in doses showing individually the greatest stimulative effect on the synthesis of beat-galactosidase, no summation of the effect of the hormones occurs in the strain E. coli 200 PS/Flac in the presence of IPTG while in the strain E. coli ML-308 simultaneous application of insulin and cortisone induces a negligible increase in the activity of beta-galactosidase. Tests for the incorporation of [3H] cortisone into the strains E. coli 200 PS/Flac and ML-308 have shown that the hormone is taken up by the bacterial cell immediately after its addition to the incubation medium, reaching its maximum after 5 min of incubation and maintaining the same level in the subsequent 30 min. The incorporation of [3H] cortisone at a temperature of 37degrees C is markedly higher than at 4degrees C. Preliminary incubation of the cultures with unlabelled cortisone and insulin resulted in a decrease in the uptake of [3H] cortisone by the bacterial cell.