Existe um grande interesse científico voltado para a busca das bases neuropsicofarmacológicas dos comportamentos que têm sido associados ao medo e ao pânico. Muitos estudos sugerem o teto mesencefálico (TM) como responsável pelo controle de respostas defensivas elaboradas durante situações de perigo iminente. A substância cinzenta periaquedutal (SCP), as camadas profundas do colículo superior (cpCS) e o colículo inferior (CI) têm sido considerados importantes estruturas na elaboração do medo inato e do comportamento de defesa, assim como na organização da antinocicepção induzida pelo medo inato. Contudo, muitos estudos têm implicado a via neoestriado-nigro-tectal no controle de respostas defensivas elaboradas no mesencéfalo dorsal, permeadas pela interação entre vias opioides e GABAérgicas. O presente trabalho tem por objetivo o estudo neurofarmacológico da anatomia conectiva funcional entre a substância negra (SN) e estruturas do TM, como a SCP e as cpCS, ligadas à organização do comportamento relacionado ao medo e à elaboração de processos antinociceptivos, avaliando-se o envolvimento da interação entre os sistemas opioide e canabinoide e a via nigro-tectal GABAérgica na modulação do comportamento de defesa e da antinocicepção induzida pelo medo evocado pela microinjeção de antagonista GABAérgico no continuum compreendido pela coluna dorsolateral da SCP e pelas cpCS. Com esse propósito, foram estudados os efeitos de microinjeções de agonistas e de antagonistas de receptores opioides ou canabinoides não-seletivos e seletivos na substância negra, parte reticulada (SNpr), sobre a antinocicepção que segue as diversas respostas comportamentais evocadas por microinjeções de bicuculina na SCPdl/cpCS de Rattus norvegicus (Rodentia, Muridae). O presente trabalho mostrou que a microinjeção do antagonista de receptores GABAA, bicuculina no TM, induziu comportamentos defensivos, elaborados concomitantemente com processos antinociceptivos, a interação entre vias opioides e aquelas mediadas por endocanaboinoides SNpr modula o comportamento de defesa organizado no mesencéfalo dorsal sem alteração na antinocicepção induzida pelo medo. O pré-tratamento na substância negra, parte reticulada com agonistas opioides e canabinoides aumentou os limiares nociceptivos e a microinjeção de antagonistas opioides e canabinoides, causou redução dos limiares nociceptivos. Esses dados sugerem uma interação entre vias opioides e endocanabinoides da SNpr, na modulação do comportamento que tem sido relacionado ao medo inato e a ataques de pânico, sendo recrutados receptores endocanaboinoides do tipo CB1 e CB2 do mesencéfalo ventral, ao lado de receptores opioides do tipo µ1 e na modulação de vias GABAérgicas de projeção nigro-tectal. / There is a great scientific interest in searching the neuropsychopharmacological bases of behavioural reactions associated to fear and panic. Many studies suggest that the mesencephalic tegmentum (MT) a mesencephalic division rich GABA, opiod and endocannabinoid containing neurons and/or receptors complex control on defensive responses during imminent danger conditions. It is also known that the periaquedutal grey matter (PAG), the deep layers of colliculus superior (cpCS) and the colliculus inferior (CI) are important structures related to innate fear and defence as well as to the organization of fear-induced antinociception. In addition neo-striatal-nigrotectal pathways are involved in the modutation of defensive responses elaborated in the dorsal midbrain, the central mesencephalic is rich in endocannabinoids. There are interactions between opioid and GABAergic pathways in these processes. The aim of this work is to study the role of the interaction between opioid anda endocannabinoide-mediated neurotransmission on the activity of GABAergic nigro-collicular pathways. Microinjections of non-selective ande selective agonist and antagonists of opioid an canabinoid receptor were performed in the SNpr before the GABAA receptor blockade in the dorsal midbrain (SCPdl/cpCS). The GABAA receptor blockade in the Mesencephalic tectum elicited vigorous defensive behaviour. This explosive escape behaviour was followed by significant antinociception. Microinjection of opioid and cannabinoid agonists in the SNpr increased the fear-induced antinociception and the treatment of the ventral midbrain with antagonists caused opposite effect .These data suggest a clear interaction between opioids and endocannabinoids pathways of the SNpr, in the modulation of the behaviour that has been related to the innate fear and the attacks of panic, being enlisted receiving endocannabinoids of type CB1 and CB2 of mesencephalic tegmentum, to the side of opioids receptors (-opioid receptor antagonist and µ1-opioid receptor antagonist) in the modulation of nigro-tectal GABAergic pathways.

Existe um grande interesse científico voltado para a busca das bases neuropsicofarmacológicas dos comportamentos que têm sido associados ao medo e ao pânico. Muitos estudos sugerem o teto mesencefálico (TM) como responsável pelo controle de respostas defensivas elaboradas durante situações de perigo iminente. A substância cinzenta periaquedutal (SCP), as camadas profundas do colículo superior (cpCS) e o colículo inferior (CI) têm sido considerados importantes estruturas na elaboração do medo inato e do comportamento de defesa, assim como na organização da antinocicepção induzida pelo medo inato. Contudo, muitos estudos têm implicado a via neoestriado-nigro-tectal no controle de respostas defensivas elaboradas no mesencéfalo dorsal, permeadas pela interação entre vias opioides e GABAérgicas. O presente trabalho tem por objetivo o estudo neurofarmacológico da anatomia conectiva funcional entre a substância negra (SN) e estruturas do TM, como a SCP e as cpCS, ligadas à organização do comportamento relacionado ao medo e à elaboração de processos antinociceptivos, avaliando-se o envolvimento da interação entre os sistemas opioide e canabinoide e a via nigro-tectal GABAérgica na modulação do comportamento de defesa e da antinocicepção induzida pelo medo evocado pela microinjeção de antagonista GABAérgico no continuum compreendido pela coluna dorsolateral da SCP e pelas cpCS. Com esse propósito, foram estudados os efeitos de microinjeções de agonistas e de antagonistas de receptores opioides ou canabinoides não-seletivos e seletivos na substância negra, parte reticulada (SNpr), sobre a antinocicepção que segue as diversas respostas comportamentais evocadas por microinjeções de bicuculina na SCPdl/cpCS de Rattus norvegicus (Rodentia, Muridae). O presente trabalho mostrou que a microinjeção do antagonista de receptores GABAA, bicuculina no TM, induziu comportamentos defensivos, elaborados concomitantemente com processos antinociceptivos, a interação entre vias opioides e aquelas mediadas por endocanaboinoides SNpr modula o comportamento de defesa organizado no mesencéfalo dorsal sem alteração na antinocicepção induzida pelo medo. O pré-tratamento na substância negra, parte reticulada com agonistas opioides e canabinoides aumentou os limiares nociceptivos e a microinjeção de antagonistas opioides e canabinoides, causou redução dos limiares nociceptivos. Esses dados sugerem uma interação entre vias opioides e endocanabinoides da SNpr, na modulação do comportamento que tem sido relacionado ao medo inato e a ataques de pânico, sendo recrutados receptores endocanaboinoides do tipo CB1 e CB2 do mesencéfalo ventral, ao lado de receptores opioides do tipo µ1 e na modulação de vias GABAérgicas de projeção nigro-tectal. / There is a great scientific interest in searching the neuropsychopharmacological bases of behavioural reactions associated to fear and panic. Many studies suggest that the mesencephalic tegmentum (MT) a mesencephalic division rich GABA, opiod and endocannabinoid containing neurons and/or receptors complex control on defensive responses during imminent danger conditions. It is also known that the periaquedutal grey matter (PAG), the deep layers of colliculus superior (cpCS) and the colliculus inferior (CI) are important structures related to innate fear and defence as well as to the organization of fear-induced antinociception. In addition neo-striatal-nigrotectal pathways are involved in the modutation of defensive responses elaborated in the dorsal midbrain, the central mesencephalic is rich in endocannabinoids. There are interactions between opioid and GABAergic pathways in these processes. The aim of this work is to study the role of the interaction between opioid anda endocannabinoide-mediated neurotransmission on the activity of GABAergic nigro-collicular pathways. Microinjections of non-selective ande selective agonist and antagonists of opioid an canabinoid receptor were performed in the SNpr before the GABAA receptor blockade in the dorsal midbrain (SCPdl/cpCS). The GABAA receptor blockade in the Mesencephalic tectum elicited vigorous defensive behaviour. This explosive escape behaviour was followed by significant antinociception. Microinjection of opioid and cannabinoid agonists in the SNpr increased the fear-induced antinociception and the treatment of the ventral midbrain with antagonists caused opposite effect .These data suggest a clear interaction between opioids and endocannabinoids pathways of the SNpr, in the modulation of the behaviour that has been related to the innate fear and the attacks of panic, being enlisted receiving endocannabinoids of type CB1 and CB2 of mesencephalic tegmentum, to the side of opioids receptors (-opioid receptor antagonist and µ1-opioid receptor antagonist) in the modulation of nigro-tectal GABAergic pathways.

Background Heroin dependence is associated with increased risk of the transmission of blood-borne viral (BBV) infections such as HIV, as a result of unsafe injecting practices. Opioid Substitution Treatment (OST) Programmes including Methadone Maintenance Treatment (MMT) programmes are a recommended way of addressing heroin dependence with the dual aims of reducing both heroin use and associated harms. However, OST programmes, particularly in prison settings, are often unavailable, in spite of large numbers of prisoners with heroin dependence and the high risk of HIV transmission in the prison setting. Little is currently known about the delivery of OST programmes within prison settings. A systematic literature review conducted within this study revealed that there are only a small number of studies from middle and lower-income countries and the perspectives of the range of stakeholders are often underrepresented. Aim and setting of this study This aim of this study was to understand the role of Methadone Maintenance Treatment (MMT) programmes within the context of HIV prevention programmes and to identify barriers and facilitators that influence the implementation, routine delivery and sustainability of methadone programmes in Indonesian prisons. Study design Three prison settings were selected as part of a qualitative case study. These comprised: a narcotics prison that provided methadone, a general prison that provided methadone, and a general prison, where there was no methadone programme. This allowed the exploration of multiple perspectives of prisoners and the diverse range of staff involved in the implementation of programmes. Interview and observational data were supplemented by data from medical case notes. Qualitative data underwent thematic analysis, with the help of framework analysis for data management. Principal findings This study found that there were many misconceptions about methadone programmes. HIV infection was not recognised as a problem and prison staff, healthcare staff and prisoners alike lacked understanding of the roles of methadone programmes. Prisoners participating in programmes were often stigmatised, while many prisoners believed methadone withdrawal was dangerous and could lead to death. These factors all contributed to low level participation, observed in both prisons with methadone programmes. Lack of confidentiality and associated stigmatisation as well as inappropriate assessment criteria also contributed to this, as did a lack of support systems. A reduction in international funding and a shift in national drug policy priorities away from the provision of methadone to drug-free Therapeutic Community (TC) programmes, together with a failure to embed methadone programmes within the daily prison routine currently pose challenges to effective implementation, delivery and programme sustainability. Conclusion Educating policy makers and practitioners could improve understanding of the roles of methadone programmes and increase support for programme delivery within prisons. It is therefore recommended that Indonesian government and prison policy focuses on ensuring effective delivery and sustainability of methadone programmes for people with heroin dependence in the prison setting.