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Alcohol-induced loss of righting reflex in mice having had free access to alcohol depends upon duration of its withdrawal
DIFFERENTIAL INVOLVEMENT OF T H E MAIN HISTOCOMPATIBILITY COMPLEX GENES INTO CONTROL OVER THE ALCOHOL-DEPRIVATION EFFECT IN CONGENIC RESISTANT MICE R. Salimov, N. Salimova, A. Ratkin, L. Shvets, and A. Maisky Institute of Pharmacology, Baltyjskaya 8, Moscow 125315, Russia
ALCOHOL-INDUCED LOSS OF RIGHTING REFLEX IN MICE HAVING HAD FREE ACCESS TO ALCOHOL DEPENDS UPON DURATION OF ITS WITHDRAWAL R. Salimov, N. Salimova, N. Shvets, L. Shvets institute of Pharmacology, Baltyjskaya 8, 125315 Moscow, Russia. Male mice (CBA x C57BL, F1) had free access to food, water and 30% alcohol (A) flavored with 0.1% saccharine and 0.02% menthol in their home cages for 8 months. After 3 days without A they had an individual 24 h choice between flavored water and A. The mice were recognized as having (HD, n=60) or lacking (LD, n=60) the short-term rise in %, intake during the first 1.5 h of renewed access (1.54-+0.11 or 0.45 +0.07 g/kg per h respectively) compared to the remaining 22.5 h (tile intake did not differ among the qroups). A weeP, later, loss of righting reflex (LRR) caused 5y acute A (5 g/kg, i.p.) was evaluated after 1, 2, or 3 days without access to A. In the control group, having had access to flavored water instead of A, latency and duration of LRR were 64-+23 and 254+ 19 s respectively. The latency of LRR was significantly elevated on 1st and 2nd, but not on 3rd, days without A in LDs (262-+42, 260-+ 44, 90 -+ 38 s)and HDs (322 + 39, 220_+46, 128 -+44 s). The duration of LRR was siclnificantly reduced on 1st and 2nd days without A in LDs (34-+ 14, 28+11, 116-+19 s) and HDs (24-+ 10, 55 -+ 14, 165 -+ 31 s). The duration of LRR was slightly higher in HDs than in LDs after three days without alcohol (t(38)=2.04, p=0.048). Thus, tolerance to A dissipates slightly faster in HD mice. In both groups, the tolerance to A approaches the level shown rsy alcoholnaive mice after 3 days without A.
The positive alcohol-deprivation effect (ADE) (a shortterm post-deprivation rise in its intake) hasbeen described in mice, rats, monkeys, and humans and considered as a measure of psychological dependence upo.n alcohol (AL). Negative ADE was described in hamsters despite the fact that they consume large amounts of free available AL. Presently, the ADE was studied in male mice of two pairs of congenic resistant strains differing only in some loci of main histocompatibility H-2 complex 0VIHC). The mice had access to food, water and 30% AL flavored with 0,1% saccharin and 0.02% menthol for 16 weeks. Then, a week before and 3 days after AL withdrawal, they had an individual choice [~etween flavored water and AL. After the deprivation the liquids intake rate was evaluated during the first 1.5 h and the last 22.5 h of renewal access. Mice of B10.D1 and B10.D1(R108) strains (each n=20), diverging in K, An, At, and ER loci of MHC, displayed no differences in AL"drifi'kinqnei'~her between strains nor due to deprivation. Mice of ]310.A(4R)and B10.AKM strains differed in E,, and D loci of MHC. B10.A(4R) strain (n=22) displayed thffdecrease in AL intake during the first 1.5 h of renewal access (0.7 + 0.13, 0.24-+ 0.08, and 0.73 -+ 0.1 g/kg per h respectively, p < 0.05), thus showing a negative ADE. Mice of B10.AKM (n=25) strain tended to increase AL intake (0.72-+0.09, 1.27-+0.39, and 0.61 -+0.16 g/kcj per h) exhibiting a positive-like ADE.
LONG ALCOHOL DEPRIVATION REDUCES THE ALCOHOL-DEPRIVATION EFFECT IN MICE R. Salimov, N. Shvets, N. Salimova I ~ ~ f Pharmacology, Baltyjskaya 8, Moscow 125315, Russia
PULSED MICROWAVES ABOLISH STARTLE RESPONSE AND GROOMING ENHANCEMENT AFTER CANCELLATION OF CHRONIC ALCOHOL. R. Salimov, N. Salimova, V. Pitchugin, V. Engovatov, N. Shvets, L. Shvets Institute of Pharmacology and Institute of Biophysics, Baltyiskaya 8, 125315 Moscow, Russia.
The alcohol-deprivation effect (ADE)(a short-term postdeprivati-on rise in its intake) has been described in rats, monkeys, and humans and considered as a measure of psychological dependence upon alcohol (AL). In AlL-preferring AA and P rat strains, peak o f the ADE occures after one-day AL deprivation (Sinclair & Li, Alcohol 6:505-509; 1989) and dissipates after one-week AL deprivation (Sinclair & Tiihonen, Alcohol 5:85-87; 1988). The ADE was described in subpopulation of hybrid mice (CBA x C57BL, F1) with peak o f it after 2-3 days without AL (Salimov & Salimova, Drug Alcohol Depend., 32:187-191; 1993). Now, we studied the effects of long AL deprivation on the ADE. The hybrid male mice had four months access to food, o o water and 30~ AL flavored with 0.1~ saccharin and 0.02% menthol in home caqes. When they then had a choice between flavored AL and" similarly flavored water after 3 days without AL, mice with ADE (n=30) drank more AL durin.q the first 1.5 h than during the last 22.5 h of renewed acces-s (1.53+0.12; 0.48+0.04-9/kg per h). Next 14 days they had free access to AL ani:l then AL was withdrawn for 14 days. Although mice, that formerly showed the ADE, drank still more AL during the first 1.5h than during the last 22.5 h of the test (1.21-+0.59 and 0.33-+0.04 g/kg per h), consumption of AL on the beginningof renewed access was reduced (P=0.01, Wilcoxon test).-l"here was no difference between drinking on the first and the last hours of renewed access in mice not showing the ADE.
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Hybrid male mice (CBA x C57BL, F1,) had free access to food, tap water and 30% alcohol (A) flavored with 0.1% saccharine and 0.02% menthol in their home cages for 10 weeks. After 3 days of A withdrawal, the mice had an individual 24 h choice between flavored A and similarly flavored water. The population was divided into two groups (each n=51), having (liD) and lacking (LD) shortterm rise in A intake on the f rst 1.5 h of renewed access (1.74+0.12 and 0.65+0.09 g/kg per h respectively) compared to the remaining 22.5 h (0.73-+0.08 and 0.93 + 0.14 g/kg per h). A week later the HDs and LDs were divided into tfiree subgroups matched for A drinking, and on the second day without A they were subjected to sham or true 5 rain exposure of 9.8 GHz pulsed microwaves (1.2 mkc pulse, averaged power density 0.03 mW/cm~, 3 or 300 ppc) followed by cross-maze exploration and acoustic (9 kHz, 108 dB, duration 0.2 c, 5 bursts every 15 c) startle response tests. On the next day an open fieldbehavior was evaluated. HDs did not differ from LDs in the measures of cross-maze exploration. The HDs were superior in the amplitude of last 3 startles in a series and in the duration of open field non-ambulatory movements. In HDs, the 300 ppc microwaves reduced the startle amplitude whereas the 3 ppc microwaves diminished the duration of open field non-ambulatory movements by the level shown by LDs.
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ALCOHOL-INDUCED LOSS OF RIGHTING REFLEX IN MICE HAVING HAD FREE ACCESS TO ALCOHOL DEPENDS UPON DURATION OF ITS WITHDRAWAL R. Salimov, N. Salimova, N. Shvets, L. Shvets institute of Pharmacology, Baltyjskaya 8, 125315 Moscow, Russia. Male mice (CBA x C57BL, F1) had free access to food, water and 30% alcohol (A) flavored with 0.1% saccharine and 0.02% menthol in their home cages for 8 months. After 3 days without A they had an individual 24 h choice between flavored water and A. The mice were recognized as having (HD, n=60) or lacking (LD, n=60) the short-term rise in %, intake during the first 1.5 h of renewed access (1.54-+0.11 or 0.45 +0.07 g/kg per h respectively) compared to the remaining 22.5 h (tile intake did not differ among the qroups). A weeP, later, loss of righting reflex (LRR) caused 5y acute A (5 g/kg, i.p.) was evaluated after 1, 2, or 3 days without access to A. In the control group, having had access to flavored water instead of A, latency and duration of LRR were 64-+23 and 254+ 19 s respectively. The latency of LRR was significantly elevated on 1st and 2nd, but not on 3rd, days without A in LDs (262-+42, 260-+ 44, 90 -+ 38 s)and HDs (322 + 39, 220_+46, 128 -+44 s). The duration of LRR was siclnificantly reduced on 1st and 2nd days without A in LDs (34-+ 14, 28+11, 116-+19 s) and HDs (24-+ 10, 55 -+ 14, 165 -+ 31 s). The duration of LRR was slightly higher in HDs than in LDs after three days without alcohol (t(38)=2.04, p=0.048). Thus, tolerance to A dissipates slightly faster in HD mice. In both groups, the tolerance to A approaches the level shown rsy alcoholnaive mice after 3 days without A.
The positive alcohol-deprivation effect (ADE) (a shortterm post-deprivation rise in its intake) hasbeen described in mice, rats, monkeys, and humans and considered as a measure of psychological dependence upo.n alcohol (AL). Negative ADE was described in hamsters despite the fact that they consume large amounts of free available AL. Presently, the ADE was studied in male mice of two pairs of congenic resistant strains differing only in some loci of main histocompatibility H-2 complex 0VIHC). The mice had access to food, water and 30% AL flavored with 0,1% saccharin and 0.02% menthol for 16 weeks. Then, a week before and 3 days after AL withdrawal, they had an individual choice [~etween flavored water and AL. After the deprivation the liquids intake rate was evaluated during the first 1.5 h and the last 22.5 h of renewal access. Mice of B10.D1 and B10.D1(R108) strains (each n=20), diverging in K, An, At, and ER loci of MHC, displayed no differences in AL"drifi'kinqnei'~her between strains nor due to deprivation. Mice of ]310.A(4R)and B10.AKM strains differed in E,, and D loci of MHC. B10.A(4R) strain (n=22) displayed thffdecrease in AL intake during the first 1.5 h of renewal access (0.7 + 0.13, 0.24-+ 0.08, and 0.73 -+ 0.1 g/kg per h respectively, p < 0.05), thus showing a negative ADE. Mice of B10.AKM (n=25) strain tended to increase AL intake (0.72-+0.09, 1.27-+0.39, and 0.61 -+0.16 g/kcj per h) exhibiting a positive-like ADE.
LONG ALCOHOL DEPRIVATION REDUCES THE ALCOHOL-DEPRIVATION EFFECT IN MICE R. Salimov, N. Shvets, N. Salimova I ~ ~ f Pharmacology, Baltyjskaya 8, Moscow 125315, Russia
PULSED MICROWAVES ABOLISH STARTLE RESPONSE AND GROOMING ENHANCEMENT AFTER CANCELLATION OF CHRONIC ALCOHOL. R. Salimov, N. Salimova, V. Pitchugin, V. Engovatov, N. Shvets, L. Shvets Institute of Pharmacology and Institute of Biophysics, Baltyiskaya 8, 125315 Moscow, Russia.
The alcohol-deprivation effect (ADE)(a short-term postdeprivati-on rise in its intake) has been described in rats, monkeys, and humans and considered as a measure of psychological dependence upon alcohol (AL). In AlL-preferring AA and P rat strains, peak o f the ADE occures after one-day AL deprivation (Sinclair & Li, Alcohol 6:505-509; 1989) and dissipates after one-week AL deprivation (Sinclair & Tiihonen, Alcohol 5:85-87; 1988). The ADE was described in subpopulation of hybrid mice (CBA x C57BL, F1) with peak o f it after 2-3 days without AL (Salimov & Salimova, Drug Alcohol Depend., 32:187-191; 1993). Now, we studied the effects of long AL deprivation on the ADE. The hybrid male mice had four months access to food, o o water and 30~ AL flavored with 0.1~ saccharin and 0.02% menthol in home caqes. When they then had a choice between flavored AL and" similarly flavored water after 3 days without AL, mice with ADE (n=30) drank more AL durin.q the first 1.5 h than during the last 22.5 h of renewed acces-s (1.53+0.12; 0.48+0.04-9/kg per h). Next 14 days they had free access to AL ani:l then AL was withdrawn for 14 days. Although mice, that formerly showed the ADE, drank still more AL during the first 1.5h than during the last 22.5 h of the test (1.21-+0.59 and 0.33-+0.04 g/kg per h), consumption of AL on the beginningof renewed access was reduced (P=0.01, Wilcoxon test).-l"here was no difference between drinking on the first and the last hours of renewed access in mice not showing the ADE.
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Hybrid male mice (CBA x C57BL, F1,) had free access to food, tap water and 30% alcohol (A) flavored with 0.1% saccharine and 0.02% menthol in their home cages for 10 weeks. After 3 days of A withdrawal, the mice had an individual 24 h choice between flavored A and similarly flavored water. The population was divided into two groups (each n=51), having (liD) and lacking (LD) shortterm rise in A intake on the f rst 1.5 h of renewed access (1.74+0.12 and 0.65+0.09 g/kg per h respectively) compared to the remaining 22.5 h (0.73-+0.08 and 0.93 + 0.14 g/kg per h). A week later the HDs and LDs were divided into tfiree subgroups matched for A drinking, and on the second day without A they were subjected to sham or true 5 rain exposure of 9.8 GHz pulsed microwaves (1.2 mkc pulse, averaged power density 0.03 mW/cm~, 3 or 300 ppc) followed by cross-maze exploration and acoustic (9 kHz, 108 dB, duration 0.2 c, 5 bursts every 15 c) startle response tests. On the next day an open fieldbehavior was evaluated. HDs did not differ from LDs in the measures of cross-maze exploration. The HDs were superior in the amplitude of last 3 startles in a series and in the duration of open field non-ambulatory movements. In HDs, the 300 ppc microwaves reduced the startle amplitude whereas the 3 ppc microwaves diminished the duration of open field non-ambulatory movements by the level shown by LDs.
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