α4-subunit containing GABAA receptors (α4-GABAARs) are often found co-assembled with δ-subunits in extrasynaptic locations on nucleus accumbens (NAc) medium spiny neurons (MSNs), were they mediate a tonic form of inhibition thought to control the excitability of the neuron. This thesis combines genetic and pharmacological techniques to explore the role of α4-GABAARs in locomotor and reward-conditioned behaviours. Activation of α4-GABAARs by systemic or intra-accumbal administration of THIP, a GABAAR agonist with a preference for δ-subunits, was able to reduce cocainepotentiated locomotor activity in wildtype but not GABAAR α4-subunit knockout mice. Similarly, the ability of repeated cocaine to induce behavioural sensitisation was unaffected in GABAAR α4-subunit knockout mice, but systemic THIP was able to reduce the sensitised increase in locomotor activity in wildtype but not knockout mice. α4-GABAARs are also able to modulate behavioural responses to reward-conditioned stimuli and their enhancement by cocaine. Deletion of GABAAR α4-subunits from dopamine D1-expressing neurons facilitated cocaine-CPP, and activation of α4- GABAARs on NAc D1-MSNs was able to attenuate cocaine-enhancement of cocaine CPP. Conversely, deletion of GABAAR α4-subunits from dopamine D2-expressing neurons increased CRf responding, and activation of α4-GABAARs on NAc D2-MSNs was able to attenuate cocaine-potentiation of CRf responding. These data also indicate that there is a dissociation in the NAc MSNs mediating cocaine-CPP and CRf responding. This may be explained by the different glutamatergic inputs needed to provide information about conditioned cues important for these behaviours. The data presented within this thesis indicate that α4-GABAAR-mediated inhibition of D1- and D2-expressing neurons plays an important physiological role in controlling behavioural responses to conditioned cues. Furthermore, NAc α4βδ GABAARs may provide a potential therapeutic target by which to limit the enhancement of locomotor and conditioned-behaviours by cocaine.

Thesis (M.A.)--University of North Carolina Wilmington, 2009. / Title from PDF title page (February 22, 2010) Includes bibliographical references (p. 55-58)

Thesis (Ph. D.)--University of Texas at Austin, 2000. / Vita. Includes bibliographical references (leaves 126-144). Available also in a digital version from Dissertation Abstracts.

Thesis (Ph. D.)--University of Wisconsin--Madison, 2005. / Includes bibliographical references (p. 296-323).

Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico / A equivalÃncia farmacÃutica entre dois medicamentos relaciona-se à comprovaÃÃo de que ambos contÃm o mesmo fÃrmaco (mesma base, sal ou Ãster da mesma molÃcula terapeuticamente ativa), na mesma dosagem e forma farmacÃutica, o que pode ser avaliado por meio de testes in vitro. No Brasil, os medicamentos alopÃticos sÃo divididos em trÃs categorias quanto ao registro junto à AgÃncia Nacional de VigilÃncia SanitÃria: medicamentos novos, medicamentos similares e medicamentos genÃricos. O objetivo foi avaliar a EquivalÃncia FarmacÃutica da Carbamazepina 200 mg (CBZ) e Diazepam 10 mg (DZP) comercializados no programa FarmÃcia Popular do Brasil, visando discutir a importÃncia da qualidade dos medicamentos para a saÃde pÃblica. Utilizou-se como SubstÃncia QuÃmica de ReferÃncia (SQR) carbamazepina e diazepam, com teor declarado de 99,6 e 99,9%, respectivamente. Realizaram-se testes fÃsico-quÃmicos tais como: determinaÃÃo de peso mÃdio, desintegraÃÃo, dureza, friabilidade, teor, uniformidade de conteÃdo e perfil de dissoluÃÃo, segundo a FarmacopÃia Brasileira (F.Bras.) 4a ediÃÃo. Os resultados indicaram uma dureza menor nos comprimidos de DZP da FarmÃcia Popular. Em relaÃÃo ao Perfil de dissoluÃÃo da CBZ, a anÃlise por ANOVA indicou haver diferenÃas significativas (p<0,05) entre os perfis de dissoluÃÃo da FarmÃcia popular em relaÃÃo ao genÃrico e referÃncia nos tempos avaliados. Comparou-se o perfil de dissoluÃÃo do comprimido da FarmÃcia Popular em relaÃÃo ao medicamento referÃncia, atravÃs dos cÃlculos dos fatores de diferenÃa (f1) e semelhanÃa (f2). Obteve-se um valor de 46,29 e 35,00, respectivamente, indicando diferenÃas nos perfis avaliados. Nos comprimidos de DZP, verificou-se que os valores de percentagem de fÃrmaco dissolvido para as trÃs amostras avaliadas, foram superiores a 85% em 15 minutos de teste, e a comparaÃÃo pelo cÃlculo dos fatores de f1 e f2, nÃo pÃde ser aplicada neste caso. Evidenciou diferenÃa (p<0,05) nos primeiros 75 minutos avaliados para as trÃs amostras, o que pode nÃo ter uma significÃncia farmacÃutica. Os outros parÃmetros fÃsico-quÃmicos cumpriram com as especificaÃÃes da F. Bras. em todas as amostras de CBZ e DZP. Portanto, os comprimidos de CBZ da FarmÃcia Popular nÃo sÃo equivalentes farmacÃuticos em relaÃÃo ao medicamento referÃncia. / Two drugs are considered pharmaceutically equivalent when both contain the same drug (base, salt or ester of the same active ingredient), at the same dosage and pharmaceutical form determined in vitro. In Brazil, the allopathic drugs are classified into three cathegories when registered in the Brazilian health surveillance agency (AgÃncia Nacional de VigilÃncia SanitÃria): new, similar or generic drugs. This work aimed to determine the pharmaceutical equivalence of Carbamazepine 200 mg (CBZ) and Diazepam 10 mg (DZP) marketed in the Brazil Popular Pharmacy program, discussing the importance of drugs for public health. Carbamazepine SQR and Diazepam SQR were used as reference drugs with 99.6 and 99.9% declared content, respectively. Physicochemical studies, such as mean weight, disintegration, hardness, friability, content, content uniformity and dissolution profile were performed in accordance to Brazilian Pharmacopeia 4th edition. The results indicated a lower hardness of DZP Popular Pharmacy tablets. Despite the dissolution profile of CBZ, the ANOVA test presented significant statistical difference (p<0.05) between Popular Pharmacy tablets and generic or reference drugs in all the time point evaluated. The dissolution profile of Popular Pharmacy and reference tablets were compared through the f1 (difference) and f2 (similarity) factors. Values of 46.29 and 35.00 respectively were found suggesting a difference on the profiles evaluated. The DZP tablets, despite the sample, showed a dissolution fraction higher than 85% in 15 minutes. f1 and f2 were not possible to be calculated in these cases. The variance analysis evidenced, for all the samples, statistical difference (p< 0.05) in the first 75 minutes evaluated, what might not have pharmaceutical importance. The other physicochemical parameters were in accordance with Brazilian Pharmacopeia for all the CBZ and DZP samples. Therefore, the CBZ tables cannot be considered pharmaceutically equivalents to the reference ones.

Background: Psychotropic medicines are widely used to treat mental illness in the community. In prisons, however, the continuity and appropriateness of prescribing for mentally ill prisoners have been questioned. There has been little research on the use of psychotropic medicines in prisons in England and Wales; yet this information is essential for determining the extent to which there is equivalence of care between prisons and the community and for effective medicines management. Aims and objectives: This study aimed to determine patterns of psychotropic prescribing in prisons and consider the extent to which people with mental illness have 'equivalent' access to psychotropic medicines in prison. Methods: A mixed methods design was used, incorporating three interrelated studies: a retrospective case note review to estimate the proportion of prescriptions for psychotropic medicines which were discontinued on entry to prison; a cross-sectional survey to estimate point-prevalence psychotropic prescribing rates in prisons, as compared with the community; and a qualitative interview study with members of prison healthcare staff and patients with mental illness to a) explore the perceived purpose of psychotropic prescribing and b) to deconstruct patient and doctor accounts of medication changes on entry to prison. Findings: Half (47%) of all psychotropic medicines reported on entry into prison were not prescribed within seven days of arrival. The cross-sectional study found that psychotropic medications were prescribed to 20% of men and 44% of women in prison; age-adjusted prescribing rates were at least five times higher in prison than in the general population. However, no valid clinical indication was recorded for half (47%) of prescriptions for psychotropic medication in prison. Qualitative analysis showed that patients interpreted the principle of equivalence differently to doctors and attributed negative outcomes to changes to medication regimes in prison. Patients reported using psychotropic medicines to reduce symptoms of mental illness, but also as a coping strategy and to reduce insomnia. Whilst staff voiced concerns regarding possible overreliance on psychotropic drugs, patients perceived insufficient access to alternative forms of treatment and support in prison. Discussion: These findings confirm high use of psychotropic medicines in prison and caution prison prescribers against abrupt withdrawal of psychotropic medicines on entry to prison, overreliance on psychotropic medicines, potentially inappropriate prescribing and poor record keeping. Strengths and limitations, implications for practice and recommendations for future work are also discussed.

This study examined psychotropic medication claims in a sample of Protestant clergy. It estimated the proportion of clergy in the sample who had a claim for psychotropic medication (i.e., anti-depressants and anxiolytics) in 2005 and examined associations between sociodemographic characteristics, occupational distress and having a claim. Protestant clergy (n = 749) from nine denominations completed a mail survey and provided access to their pharmaceutical records. Logistic regression models assessed the effect of sociodemographic characteristics and occupational distress on having a claim. The descriptive analysis revealed that 16 % (95 % Confidence interval [CI] 13.3 %-18.5 %) of the clergy in the sample had a claim for psychotropic medication in 2005 and that, among clergy who experienced frequent occupational distress, 28 % (95 % CI 17.5 %-37.5 %) had a claim. The regression analysis found that older clergy, female clergy, and those who experienced frequent occupational distress were more likely to have a claim. Due to recent demographic changes in the clergy population, including the increasing mean age of new clergy and the growing number of female clergy, the proportion of clergy having claims for psychotropic medication may increase in the coming years. To the best of our knowledge, this is the first study to examine the use of psychotropic medication among clergy.

This study examined psychotropic medication claims in a sample of Protestant clergy. It estimated the proportion of clergy in the sample who had a claim for psychotropic medication (i.e., anti-depressants and anxiolytics) in 2005 and examined associations between sociodemographic characteristics, occupational distress and having a claim. Protestant clergy (n = 749) from nine denominations completed a mail survey and provided access to their pharmaceutical records. Logistic regression models assessed the effect of sociodemographic characteristics and occupational distress on having a claim. The descriptive analysis revealed that 16 % (95 % Confidence interval [CI] 13.3 %-18.5 %) of the clergy in the sample had a claim for psychotropic medication in 2005 and that, among clergy who experienced frequent occupational distress, 28 % (95 % CI 17.5 %-37.5 %) had a claim. The regression analysis found that older clergy, female clergy, and those who experienced frequent occupational distress were more likely to have a claim. Due to recent demographic changes in the clergy population, including the increasing mean age of new clergy and the growing number of female clergy, the proportion of clergy having claims for psychotropic medication may increase in the coming years. To the best of our knowledge, this is the first study to examine the use of psychotropic medication among clergy.

No description available.

No description available.