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2 Neurobiologia di genere e dipendenzeDipartimento di Scienze Biomediche Università degli Studi di Cagliari Istituto di Neuroscienze del CNR Neurobiologia di genere e dipendenze Matera, SITD,Ottobre 2016

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4 The italian picture by gender: alcohol

5 The italian picture by gender: illicit drugs

6 The italian picture by gender: doping

7 Past month cigarette use by gender

8 Binge alcohol use by gender

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10 Marijuana use by gender

11 Marijuana use by gender

12 Organizzazione dei neuroni dopaminergicimeso-corticali

13 Testosterone controls burst firingin the VTA DA-PFCX circuit

14 Testosterone specifically controls burst firing of VTA DA neuronsSN DA neurons

15 Testosterone specifically controls burst firing of PFCX to VTA neuronsNon PFCX to VTA neurons PFCX to VTA neurons

16 Control of PFCX DA by GABA-B &GLU receptorsAMPA antagonist NBQX

17 Opposite effects of APV on PFCX DANMDA antagonist

18 Strongher effects of CGP52432 on PFCX DA in femaleGABA B antagonist

19 Differential organization of GLU-GABA-B interaction on PFCX DA in males and females Males Tonic NMDA Tonic AMPA GABA-B interneurons PFCX to VTA neurons ______________________________________ Females Tonic NMDA Tonic AMPA

20 Impulsivity measures

21 Impulsive action Stop task

22 Impulsive action by gender

23 Impulsive action: summaryNormal Inconsistent evidence for sex differences. When sex differences are observed, the direction of the difference depends in part on the task administered (i.e., men display poorer control on go/no-go and CPT tasks,whereas women display poorer control on stop tasks). Abuse Among heavy drinkers and smokers, women exhibit greater impulsive action than do men De Wit, 2014

24 Impulsive choice

25 Impulsive choice by gender

26 Impulsive choice: summaryNormal Women show greater impulsive choice for hypothetical rewards, whereas men may show greater impulsive choice for actual rewards. Abuse Sex differences in impulsive choice do not appear to differ between smokers and non-smokers. Greater impulsive choice might be associated with increased genetic risk for alcoholism specifically in women. .

27 in behavioral components of impulsivity.Impulsivity , gender and drug abuse: overall conclusions Current knowledge regarding gender differences in impulsivity and associations between impulsivity and drug abuse is lacking. Well-controlled, adequately powered studies are necessary to gain a more complete picture of the degree to which males and females differ in behavioral components of impulsivity.

28 Positron Emission Tomography (PET): local blood flow Functional Brain Imaging Positron Emission Tomography (PET): local blood flow Tomografia ad Emissione di Positroni: flusso ematico locale Functional Magnetic Resonance Imaging (fMRI): BOLD* signal Risonanza Magnetica Funzionale *Blood oxigen level-dependent signal (segnale dipendente dalla concentrazione di Ossigeno nel sangue)

29 Brain default mode (Modalità di default del cervello)

30 AREE CEREBRALI NELLE QUALI IL FLUSSO EMATICO DIMINUISCE RISPETTOALLO STATO DI RIPOSO DURANTE UN TASK VISIVO (SHULMAN ET AL, 2007)

31 Shulman et al, 1995 IPL LTC PCC/Rsp dMPFC vMPFC HF+

32 Le aree del Default Networksi attivano e disattivano in maniera sincrona e parallela tra loro ma in maniera opposta e antiparallela rispetto alle aree dell’attenzione visiva

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35 Control Network Attention Network Default Network

36 Funzioni del default network

37 MEMORIA AUTOBIOGRAFICAPENSARE IL FUTURO TEORIA DELLA MENTE SCELTE ETICHE

38 Resting state fMRI In condizioni basali le aree cerebrale mostrano un’attività oscillatoria a bassa frequenza (<0.1Herz). Aree funzionalmente connesse si attivano in maniera sincrona costituendo altrettante reti neurali.

39 3 extrinsic (somatomotor, SMN, visual, VN, auditory,AN) ; Main networks 3 extrinsic (somatomotor, SMN, visual, VN, auditory,AN) ; 4 intrinsic ( default, DN; dorsal, DAN & ventral, VAN attention; fronto-parietal control , FPCN) DN AN SMN DAN VN VAN FPCN

40 Functional brain networks

41 There were no significant differences between sexes in the functional connectivity of the brain areas within the ECN, SN, or the DMN. These important findings highlight the robustness of intrinsic connectivity of these resting state networks and their similarity between sexes.

42 Default network

43 Executive network

44 Salience network

45 No significant differences between sexes in the functional connectivity of the brain areas within the ECN, SN, or the DMN. These findings highlight the robustness of intrinsic connectivity of these resting state networks and their similarity between sexes.

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47 Working memory-related activations: female>male

48 Areas of interaction between Working memory and Negative emotion

49 Male Female

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51 These findings imply parallel processing of emotion and cognition in females and mutually interacting processing in males.

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53 SPM results for the “normalized” metabolic images for Neutral vs Cocaine-cues video conditions in the Females. Volkow ND, Tomasi D, Wang GJ, Fowler JS, Telang F, et al. (2011) Reduced Metabolism in Brain “Control Networks” following Cocaine-Cues Exposure in Female Cocaine Abusers. PLoS ONE 6(2): e doi: /journal.pone

54 SPM results for the gender by cues (Neutral > Cocaine-cues) interaction on the “normalized” metabolic images. Volkow ND, Tomasi D, Wang GJ, Fowler JS, Telang F, et al. (2011) Reduced Metabolism in Brain “Control Networks” following Cocaine-Cues Exposure in Female Cocaine Abusers. PLoS ONE 6(2): e doi: /journal.pone

55 Cingulo-opercular Fronto-parietal

56 Functions of control sub-systems