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P.5.015 Peculiarities of drug addiction and alcoholism for the aborigines of the North of Russia
P.5 Addiction microiontophoresis across two different ejection current ranges (<30 nA and >30 nA). Reserpine (10 mg/kg i.p.) was administered to six animals five hours before the recording sessions. Cocaine induced a decrease in spontaneous activity with the glutamate-evoked excitation unaffected resulting in an increase in signal to noise ratio (<30 nA = 25%, n = 24 and >30 nA = 31%, n = 13). Procaine (n = 24) also produced an increase in signal to noise ratio, however, overall, was less effective than cocaine in potentiating glutamate-evoked excitation. In reserpinized animals (n = 17) cocaine diminished glutamate excitation with no changes in spontaneous activity. These results suggest that both cocaine and procaine can have facilitatory actions in the cerebellum which could be at least partially dependent upon endogenous NE pools. (Supported by DA07175, RCMI 03035 and GM50695 to CAJR).
subanaesthetic dose of ketamine can be used in ketamine-assisted psychotherapy of alcohol dependence (Krupitsky et al., 1992; Krupitsky and Grinenko, 1996).
References 1 ] Krupitsky E.M., Grinenko A.Y., Berkaliev T.N., Palei A.I., Petrov V.N., Borodkin Y.S. (1992) The combination of psychedelic and aversive approaches in alcoholism treatment: The affective contra-attribution method. Alcoholism Treatment Quarterly 9: 99-105. I21 KrupitskyE.M. and Grinenko A.Y. (1996) Ketaminepsychedelic psychotherapy of alcoholism. Alcoholism: Clinical and Experimental Research 20 (Suppl): 90A.
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Peculiarities of drug addiction and alcoholism for the aborigines of the North of Russia
E.A. Krivogornitsina. Medical Institute of Yakutsk, State Universit3;
677005 Yakutsk Sakha Republic, Russia This study was made with the purpose to compare clinical peculiarities and biochemical data for different forms of alcoholism and drug addiction in different Yakutia inhabitants ethnical groups with clinical and biochemical research methods appliance. 55 patient (45 males and 10 females, 25-30 years old) - alcoholics, opium and hashish addicts - were examined. The duration of addiction was within the range of 5-7 years. The study revealed quick and more malignant addiction, more severe obstinent syndrome development for the Yakutia aborigines (different nationalities of Mongoloid race: Yakuts, Evenks, Dolgans, Yukagirs) as compared to those of European origin (Russians, Ukrainians, Byelorussians). Heavier symptoms of obstinent syndrome demanded more intensive pharmacologic therapia for the Yakutiya aborigines treatment. Biochemical blood analysis discovered that the content of ferments reacting with the drugs appeared to be much lower in the blood of the North aborigines than in the blood of the Europeans. These data allows to suppose that among the reasons for quick addiction and heavier obstinent syndrome of the Yakutia aborigines low activity of ferments responsible for drug and alcohol withdrawal plays one of the leading roles.
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Nimodipine attenuate memory disturbances caused by subanaesthetic dose of ketamine in sober alcoholic patients
E.M. Krupitsky, V.B. Ivanov, L.S. Priputina, A.Y. Grinettko. Research
laboratoQ', St. Petersburg Regional Dispensary of Narcology, Novo-Deviatkino 19/1, Leningrad Region 188661, Russia Both ketamine and ethanol block, with varying potency, the actions of glutamate at the N-methyl-D-aspartate (NMDA) receptor. Nimodipine has shown efficacy in alcohol detoxification. The study of the influence of dihydropyridine calcium channel blocker, nimodipine, on memory disturbances caused by NMDA-receptor calcium channel blocker, ketamine, could provide important information about the underlying mechanisms of memory disturbances caused by alcohol and contribute to the alcoholism therapy. In this study 24 detoxified alcoholic patients had been randomly assigned to one of two groups (12 patients in the each of the groups). Patients of the experimental group received nimodipine (60 mg a day orally) for two days and also the same dose of nimodipine in four hours prior to injection of subanaesthetic dose of ketamine (2.25 mg/kg of body weight intramuscularly). Patients of the control group received placebo prior to ketamine injection. Five digits delayed recall test was employed: Patients of both groups were required to remember five digits pronounced during the one hour of ketamine-induced altered state of consciousness (first hour after the ketamine injection). The study design was double-blind, placebo-controlled and randomized. In two hours after the ketamine injection all patients were back in normal consciousness. At that time patients of the experimental group were able to remember 3.4 ± 0.6 digits while patients of control group 1.2 ± 0.4 (p < 0.0l). Thus, nimodipine attenuate memory disturbances induced by ketamine. The ability of nimodipine to reverse memory disturbances caused by
$257
Early weaning and manipulation of social milieu during pre-puberty affect cocaine reinforcing properties in adult mice
G. Laviola, G. Dell'Omo. Section of Behavioral Pathophysiology, Labor.
F.O.S., lstituto Superiore di San#& Roma, Italy The aim of this study was to determine in mice if manipulation of weaning time and of social variables during pre-puberty would account for the individual features of behavior that are correlated with the abuse of drugs. This issue was addressed by searching for differences in cocaine effects in the adult offspring of both sexes from outbred Swiss CD-1 mouse litters. On postnatal day 15, litters were split in two halves, with one half litter weaned (Precocious weaning, PWI while the other remained with the dam (Regular weaning, RW). At the same time, pups in each half litter were assigned to either a unisex or a mixed-sex rearing condition. Since postnatal day 25 to adulthood (>70 postnatal days, time of testing), all mice were re-housed according to both sex and weaning. Both adult PW male mice and unisex-reared animals of both sexes were in general more active than corresponding controls. In a place conditioning schedule, aimed at assessing the reinforcing properties of cocaine HCI (two drug pairings; 0, 1, or 5 mg/kg, IP), mixed-sex mice cff both sexes were readily conditioned by the drug. Time of weaning determined the direction of the conditioned performance. In fact, whereas RW mice showed in this specific paradigm a reduction of time spent in the drug-paired area, subjects weaned precociously developed a quite clear conditioned place preference in a dose-dependent fashion. Interestingly, irrespective of their weaning history, cocaine failed to induce conditioning in animals which underwent sexual segregation during development. These differential cocaine effects i) suggest alterations in the function of mesolimbic and nigrostriatal DA systems linked to subtle changes in social stimulation during development, and ii) may be associated with an acquired predisposition to exhibit an individual respons[vity to drugs of abuse.
References [ 1] Laviola & Loggi (1992). Sexual segregationin infancy and bidiretional benzodiazepine effects on hot-plate response and neophobia in adult mice. Pharmacology Bioehemist~ & Behavior, 42: 865-870. [2] Loggi, Dell'Omo & Laviola (1996) Individual differences in response to psychological stress and chlordiazepoxide in adult mice: Relations with changes in early scxzialmilieu. Psychobiology,24: 147-153. [3] Terranova& Laviola (1995). Individual differences in mouse behavioral development: Effects of precociousweaning and ongoing sexual segregation.Animal Behavior, 50: 1261-1271.
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Electrophysiological evidence for enhanced processing of drug-related stimuli in opiate users D.I. Lubman 1, A. Chen 2, J.F.W. De',~dn 1. 1Departmeni! of Psychiatry Universi~' of Manchester, Oxford Road, Manchester, MI3 9WL; 2Hope Hospital, Fccles Old Road, Salford, Manchester M6 8HD, England Introduction: Several studies have reported that stimul!i associated with taking heroin acquire the ability to elicit craving in dependent subjects and after withdrawal. This may be a mechanism of relapse. We have used event-related potentials (ERPs) to investigate the brain mechanisms involved. Methods: Subjects included 20 opiate-dependent and 13 drug treatment workers. The drug workers understood the drug cues but none
subanaesthetic dose of ketamine can be used in ketamine-assisted psychotherapy of alcohol dependence (Krupitsky et al., 1992; Krupitsky and Grinenko, 1996).
References 1 ] Krupitsky E.M., Grinenko A.Y., Berkaliev T.N., Palei A.I., Petrov V.N., Borodkin Y.S. (1992) The combination of psychedelic and aversive approaches in alcoholism treatment: The affective contra-attribution method. Alcoholism Treatment Quarterly 9: 99-105. I21 KrupitskyE.M. and Grinenko A.Y. (1996) Ketaminepsychedelic psychotherapy of alcoholism. Alcoholism: Clinical and Experimental Research 20 (Suppl): 90A.
I - ~ ~
Peculiarities of drug addiction and alcoholism for the aborigines of the North of Russia
E.A. Krivogornitsina. Medical Institute of Yakutsk, State Universit3;
677005 Yakutsk Sakha Republic, Russia This study was made with the purpose to compare clinical peculiarities and biochemical data for different forms of alcoholism and drug addiction in different Yakutia inhabitants ethnical groups with clinical and biochemical research methods appliance. 55 patient (45 males and 10 females, 25-30 years old) - alcoholics, opium and hashish addicts - were examined. The duration of addiction was within the range of 5-7 years. The study revealed quick and more malignant addiction, more severe obstinent syndrome development for the Yakutia aborigines (different nationalities of Mongoloid race: Yakuts, Evenks, Dolgans, Yukagirs) as compared to those of European origin (Russians, Ukrainians, Byelorussians). Heavier symptoms of obstinent syndrome demanded more intensive pharmacologic therapia for the Yakutiya aborigines treatment. Biochemical blood analysis discovered that the content of ferments reacting with the drugs appeared to be much lower in the blood of the North aborigines than in the blood of the Europeans. These data allows to suppose that among the reasons for quick addiction and heavier obstinent syndrome of the Yakutia aborigines low activity of ferments responsible for drug and alcohol withdrawal plays one of the leading roles.
•
Nimodipine attenuate memory disturbances caused by subanaesthetic dose of ketamine in sober alcoholic patients
E.M. Krupitsky, V.B. Ivanov, L.S. Priputina, A.Y. Grinettko. Research
laboratoQ', St. Petersburg Regional Dispensary of Narcology, Novo-Deviatkino 19/1, Leningrad Region 188661, Russia Both ketamine and ethanol block, with varying potency, the actions of glutamate at the N-methyl-D-aspartate (NMDA) receptor. Nimodipine has shown efficacy in alcohol detoxification. The study of the influence of dihydropyridine calcium channel blocker, nimodipine, on memory disturbances caused by NMDA-receptor calcium channel blocker, ketamine, could provide important information about the underlying mechanisms of memory disturbances caused by alcohol and contribute to the alcoholism therapy. In this study 24 detoxified alcoholic patients had been randomly assigned to one of two groups (12 patients in the each of the groups). Patients of the experimental group received nimodipine (60 mg a day orally) for two days and also the same dose of nimodipine in four hours prior to injection of subanaesthetic dose of ketamine (2.25 mg/kg of body weight intramuscularly). Patients of the control group received placebo prior to ketamine injection. Five digits delayed recall test was employed: Patients of both groups were required to remember five digits pronounced during the one hour of ketamine-induced altered state of consciousness (first hour after the ketamine injection). The study design was double-blind, placebo-controlled and randomized. In two hours after the ketamine injection all patients were back in normal consciousness. At that time patients of the experimental group were able to remember 3.4 ± 0.6 digits while patients of control group 1.2 ± 0.4 (p < 0.0l). Thus, nimodipine attenuate memory disturbances induced by ketamine. The ability of nimodipine to reverse memory disturbances caused by
$257
Early weaning and manipulation of social milieu during pre-puberty affect cocaine reinforcing properties in adult mice
G. Laviola, G. Dell'Omo. Section of Behavioral Pathophysiology, Labor.
F.O.S., lstituto Superiore di San#& Roma, Italy The aim of this study was to determine in mice if manipulation of weaning time and of social variables during pre-puberty would account for the individual features of behavior that are correlated with the abuse of drugs. This issue was addressed by searching for differences in cocaine effects in the adult offspring of both sexes from outbred Swiss CD-1 mouse litters. On postnatal day 15, litters were split in two halves, with one half litter weaned (Precocious weaning, PWI while the other remained with the dam (Regular weaning, RW). At the same time, pups in each half litter were assigned to either a unisex or a mixed-sex rearing condition. Since postnatal day 25 to adulthood (>70 postnatal days, time of testing), all mice were re-housed according to both sex and weaning. Both adult PW male mice and unisex-reared animals of both sexes were in general more active than corresponding controls. In a place conditioning schedule, aimed at assessing the reinforcing properties of cocaine HCI (two drug pairings; 0, 1, or 5 mg/kg, IP), mixed-sex mice cff both sexes were readily conditioned by the drug. Time of weaning determined the direction of the conditioned performance. In fact, whereas RW mice showed in this specific paradigm a reduction of time spent in the drug-paired area, subjects weaned precociously developed a quite clear conditioned place preference in a dose-dependent fashion. Interestingly, irrespective of their weaning history, cocaine failed to induce conditioning in animals which underwent sexual segregation during development. These differential cocaine effects i) suggest alterations in the function of mesolimbic and nigrostriatal DA systems linked to subtle changes in social stimulation during development, and ii) may be associated with an acquired predisposition to exhibit an individual respons[vity to drugs of abuse.
References [ 1] Laviola & Loggi (1992). Sexual segregationin infancy and bidiretional benzodiazepine effects on hot-plate response and neophobia in adult mice. Pharmacology Bioehemist~ & Behavior, 42: 865-870. [2] Loggi, Dell'Omo & Laviola (1996) Individual differences in response to psychological stress and chlordiazepoxide in adult mice: Relations with changes in early scxzialmilieu. Psychobiology,24: 147-153. [3] Terranova& Laviola (1995). Individual differences in mouse behavioral development: Effects of precociousweaning and ongoing sexual segregation.Animal Behavior, 50: 1261-1271.
I
•
Electrophysiological evidence for enhanced processing of drug-related stimuli in opiate users D.I. Lubman 1, A. Chen 2, J.F.W. De',~dn 1. 1Departmeni! of Psychiatry Universi~' of Manchester, Oxford Road, Manchester, MI3 9WL; 2Hope Hospital, Fccles Old Road, Salford, Manchester M6 8HD, England Introduction: Several studies have reported that stimul!i associated with taking heroin acquire the ability to elicit craving in dependent subjects and after withdrawal. This may be a mechanism of relapse. We have used event-related potentials (ERPs) to investigate the brain mechanisms involved. Methods: Subjects included 20 opiate-dependent and 13 drug treatment workers. The drug workers understood the drug cues but none