Ålder, kön och konsumtionsmönster ur ett prekliniskt perspektiv
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1 Ålder, kön och konsumtionsmönster ur ett prekliniskt perspektiv SAD Erika Roman Uppsala University Medicine & Pharmacy
2 Data from unpublished studies have been removed from this presentation Medicine & Pharmacy
3 Homologous behavioral responses Sweet taste Bitter taste Peciña S et al., 2006
4 Brain reward networks The mesocorticolimbic dopamine system Evolutionary conserved across species
5 Activation by natural rewards Fonzies Chocolate time (min) Bassareo & Di Chiara 1997 Bassareo et al 2002
6 Nucleus accumbens activation during orgasm in women Wise et al., 2017 Pfaus et al., 1990
7 Comparison human versus rat Homo sapiens Rattus norvegicus Gestation 270 days 22 days Infant 0-24 months 0-21 days Adolescence years 4-8 weeks Adulthood 20 years 10 weeks
8 Developmental stages in the rat Rat Human Herlenius & Lagercrantz, 2004
9 Developmental stages in the rat PND Week NB Juvenile Adult Infant Adolescence puberty puberty Adolescence: Adulthood: 10.5 rat days = 1 human year 11.8 rat days = 1 human year Lundberg, 2017 Andreollo et al., 2012
10 Research animal depending on questions Outbred stocks Genetic heterogeneity Individual differences Inbred strains Brother x sister mating Genetic homogeneity Selectively bred lines E.g. alcohol-preferring/alcohol nonpreferring
11 Face validity Validity of animal models Similar symptoms and phenomenon's I.e. the degree of descriptive similarity between the behavioral abnormalities seen in the model system and the clinical condition Construct validity Similar underlying mechanisms I.e. mechanistic similarities between the model and the clinical condition Predictive validity The model allows extrapolation from one species to another, including humans, and from one condition to another Response to pharmacological treatment Problems with validity in many psychiatric disorders BUT good in addiction research
12 Dietary preferences in rats 1750 Energy intake kj / kg body wt and day Carbohydrates Protein Fat High-CHO High-prot High-fat Fat Protein Carbohydrates Alsiö J et al., 2009
13 Sexual behavior in selectively bred alcoholpreferring and non-preferring rats Karlsson O et al., 2015
14 Gambling strategies in rats The rat Gambling Task has been established Rats with strategic as well as risky gambling strategies can be distinguished Tjernström el al., analysis in progress
15
16 Adult males and females No difference in behavioral profiles between adult male and female rats Males Females Meyerson BJ et al., 2006
17 Adult versus adolescent male rats Adult Functional categories: General activity Exploratory activity Risk assessment Risk taking Shelter seeking Adolescent rats Risk assessment is less pronounced in adolescent rats Three behavioral types can be distinguished Meyerson et al., 2013 Lundberg et al., in manuscript
18 Home cage voluntary alcohol intake Voluntary drinking in the home cage Free access to ethanol solution, water and food 2-bottle free choice (ethanol solution and water) Continuous access Intermittent access; 24 h, Mo, We, Fri
19 Research animal depending on questions Outbred stocks Genetic heterogeneity Individual differences Inbred strains Brother x sister mating Genetic homogeneity Selectively bred lines E.g. alcohol-preferring/alcohol nonpreferring
20 Selective breeding for contrasting alcohol intake Wistar rats foundation stock Bidirectional selection for alcohol preference and intake (selected phenotype), in two opposite directions, over successive generations until the selection plateau has been reached: > 5-6 g/kg alcohol/day in preferring rats < 0.5 g/kg alcohol/day in non-preferring rats Daily voluntary alcohol intake Alcohol-preferring rats Alcohol non-preferring rats Courtesy: Giancarlo Colombo
21 Selective breeding for contrasting alcohol intake Alcohol-preferring Alkoholintag (g/kg/dag) Females Males Generation Roman E, Beroendemedicin 2015 Courtesy: Nicholas Grahame, IUPUI
22 Behavioral profiling of multiple pairs of selectively bred alcohol-preferring male rats Mean sum rank AA P sp HAD1 HAD2 Finland USA Italy USA USA 50 0 General activity Exploration Risk assessment Risk taking Shelter seeking No common behavioral profile associated with high alcohol intake and preference Roman E et al., Addict Biol 2012
23 Adult selectively bred alcohol-preferring rats 7 Selectively bred alcohol-preferring AA rats 6 Females Ethanol intake (g/kg/day Male AA Female AA Males % EtOH 10% EtOH Modified from Roman E et al., 2005
24 Adult selectively bred alcohol-preferring rats Selectively bred alcohol-preferring sp rats First hour 24 h Loi B et al., 2014
25 Research animal depending on questions Outbred stocks Genetic heterogeneity Individual differences Inbred strains Brother x sister mating Genetic homogeneity Selectively bred lines E.g. alcohol-preferring/alcohol nonpreferring
26 Behavioral sensitization to nicotine 5 weeks of age 10 weeks of age 36 weeks of age Adermark L et al., 2015
27 Importance of studying subgroups Intermittent access 20% EtOH and water Six weeks Momeni S et al. 2015
28 Alcohol intake in adult males and females Refinement of housing conditions in studies of voluntary alcohol intake Higher voluntary alcohol intake in females than in males Photo: Sara Palm
29 Alcohol-induced effects on behavior in adult males Total activity Rearings Karlsson O & Roman E, 2016
30 Summary Larger focus on females, especially female subgroups Differences between adolescents and adults Adolescence is short in rats Much remains to be studied in females adolescents Medicine & Pharmacy
31 Thank you for your attention! VR-MH, ERAB, SRA, Svenska Spel Research Council, Facias Foundation Bertil Göransson scholarship Medicine & Pharmacy
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