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Home > Neuropharmacological Studies in Rat Models on Morphine and Nalbuphine Induced Addiction, Anti-Nociception and Serotonin-1A Receptor Expression for Improving Therapeutics in Pain

Neuropharmacological Studies in Rat Models on Morphine and Nalbuphine Induced Addiction, Anti-Nociception and Serotonin-1A Receptor Expression for Improving Therapeutics in Pain

Thesis Info

Access Option

External Link

Author

Nawaz, Shazia

Program

PhD

Institute

University of Karachi

City

Karachi

Province

Sindh

Country

Pakistan

Thesis Completing Year

2018

Thesis Completion Status

Completed

Subject

Molecular Medicine

Language

English

Link

http://prr.hec.gov.pk/jspui/bitstream/123456789/12762/1/Shazia%20Complete%20PhD%20Thesis.docx

Added

2021-02-17 19:49:13

Modified

2024-03-24 20:25:49

ARI ID

1676726749030

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Morphine and other opioids are the most effective prescription medications for the treatment of pain. Associated addiction and hyperalgesia, however, limits the clinical utility of these drugs. The present study aimed to determine the potential effectiveness of buspirone, a partial agonist at 5-hydroxytryptamine (5-HT, serotonin)-1A receptor in reducing morphine-induced addiction and hyperalgesia. We found that co-administration of buspirone with morphine inhibited reinforcing as well as hyperalgesic effects of morphine. Tolerance in motor depressant effects of morphine was also reversed. Effects of morphine on dopamine and serotonin metabolism in nucleus accumbens and caudate were also reversed by buspirone co-administration. Reinforcing, analgesic, and motor effects of nalbuphine, another opioid drug, were also monitored. Both low and high doses of nalbuphine produced reinforcing effects. High but not low doses produced sensitization. Moderate doses of nalbuphine did not produce reinforcement or sensitization like effects. Moderate doses of nalbuphine produced greater pain killing effects than smaller or higher doses. We also determined the effects of repeated administration of buspirone on memory, pain perception, and 5-HT1A receptor expression in brain regions associated with addiction and memory. Administration of buspirone at 1 mg/kg but not at 0.3 mg/kg or 0.1 mg/kg produced significant analgesic effects. Repeated administration of buspirone at doses of 0.1 and 1 mg/kg but not at 0.3 mg/kg produced hyperalgesia. Low buspirone dosage (0.1 mg/kg) improved, while higher dosages (0.3 and 1 mg/kg) impaired performance in Morris water maze. This was associated with the down-regulation of serotonin-1A receptors in the prefrontal cortex and hippocampus. The findings show an important role of 5-HT1A receptor in morphine abuse and hyperalgesia. It is suggested that clinicians should consider buspirone as adjunctive therapy with morphine to prevent its abuse during the treatment. Because higher but not lower doses of buspirone were found to impair cognition; lower doses may be preferably used to improve therapeutics in chronic pain.
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آن لائن لیکچر

آن لائن لیکچر

شاہد اشرف

گزشتہ ایک برس کے دوران میں کووڈ کی وجہ سے آن لائن لیکچر دیتے ہوئے وہ کئی تجربات سے گزرا۔ پہلے پہل وہ اپنے دھیان میں لیکچر دیتا رہا۔ کچھ دنوں بعد اسے کیمرہ آف ہونے کے باوجود سٹوڈنٹس کی موجودگی اور عدم موجودگی کا اندازہ ہونے لگا۔ کبھی کبھی وہ کسی طالب علم کی موجودگی کی تصدیق کے لیے سوال بھی پوچھ لیتا تھا اور اس کا اندازہ درست نکلتا تھا۔ آہستہ آہستہ اسے مکمل ادراک ہونے لگا کہ کیمرہ آف ہونے کے باوجود کون سٹوڈنٹ موجود ہے اور کون لنک جوائن کرنے کے بعد سو گیا ہے ۔ ذہنی رابط برقی رابطے سے زیادہ موثر محسوس ہونے لگا۔ وہ کیمرہ آف ہونے کے باوجود دیکھنے پر قادر ہو گیا۔ کسی سٹوڈنٹ کا تصور کرتے ہی اس چہرے پر ہویدا اداسی ، بیزاری ، انہماک، دلچسپی اور نیم دلی سمیت دیگر کیفیات کا انکشاف ہونے لگتا تھا۔ وہ صرف غور سے آئی ڈی کی طرف دیکھتا اور سٹوڈنٹ کی ذہنی کیفیت ظاہر ہو جاتی۔ وہ مخاطب ہوئے بغیر کسی سٹوڈنٹ کی کیفیت پر رائے دیتا اور پھر متعلقہ سٹوڈنٹ کی حیرت کو انجوائے کرتا تھا۔ وہ دوران تدریس بہت سے تجربات سے گزرا ۔ اس کے دل میں ایک خیال زور پکڑنے لگا ۔ اس نے خیال کو جھٹکنے کی کوشش کی مگر ناکام رہا۔ اسی خیال کے زیرِ اثر ایک دن اس نے تمام سٹوڈنٹس کو کیمرے آن کرنے کا کہا ۔ سٹوڈنٹس اپنے اپنے کیمرے آن کر بیٹھ گئے ۔ وہ سب کو دیکھ سکتا تھا مگر اسی لمحے اسے شدید دھچکا لگا ۔ وہ کسی بھی سٹوڈنٹ کی کیفیت کو پڑھنے سے قاصر تھا ۔

 

 

 

An Analysis of Sociocultural Barriers on Social Empowerment of Women in Sahiwal Division

The paper sets out to discuss impact of socio-cultural barriers on social empowerment of rural women in term of decision making related to their personal as well as social life in Sahiwal division. Pakistan is a patriarchal society characterized by patri-local residence and exclusion of women from the right of inheritance and succession, which pave ways for male-headed society. In addition, socio-cultural factors strongly favour male-dominance and an inferior status of females in all walks of life. A quantitative approach was adopted for carrying out current study. A survey instrument was designed and employed for data collection from 384 respondents from rural areas of Sahiwal division. The findings of the study revealed that less than one third (31.25%) of the respondents were consulted in decision-making about domestic matters. Likewise, more than half (51.8%) of the respondents were not independent in moving out of home for meeting any social need. Similarly, more than one third (41.4%) of the respondents were not free to visit their friends in the neighborhood. The study concludes that women in the rural areas are less empowered and still suffering socially, economically and psychologically in their day to day life. The study provides an insight for professional social workers, policy makers and stakeholders in public and private sectors for influencing policy-making and planning for revisiting and redesigning existing policies and plans intended for empowerment of rural women in Pakistan

Rare Semileptonic B Meson Decays Beyond the Standard Model

In this thesis the exclusive rare semileptonic decays of B-mesons have been studied beyond the Standard ∗ Model. In particular the decays B → K1 (1270, 1400)l+ l− and Bc → Ds l+ l− are considered. These decays are induced by flavor changing neutral current (FCNC) transitions which at quark level arises as b → sl+ l− . In the Standard model these FCNC decays are not allowed at tree level but are allowed at loop level through Glashow-Iliopoulos-Maiani (GIM) mechanism. In addition they are also suppressed in the Standard Model due to their dependence on weak mixing angles of the quark flavor rotation matrix- the Cabibo Kobayashi Maskawa (CKM) matrix. These two circumstances make the FCNC decays relatively rare and hence are important to study physics beyond the Standard Model, commonly known as new physics. The main points of this thesis are: • The implications of the fourth generation quarks in the decay B → K1 (1270, 1400)l+ l− with l = μ, τ are studied, where the mass eigenstates K1 (1270) and K1 (1400) are mixture of 1 P1 and 3 P1 states with the mixing angle θK . In this context, we have studied various observables like branching ratio (BR), forward-backward asymmetry (AF B ) and longitudinal and transverse helicity fractions (fL,T ) of K1 meson in B → K1 l+ l− decays. To study these observables, we have used the Light Cone QCD sum rules form factors and set the mixing angle θK = −34◦ . It is noticed that the BR is suppressed for K1 (1400) as a final state meson compared to that of K1 (1270). Same is the case when the final state leptons are tauons rather than muons. In both the channels all of the above mentioned observables are quite sensitive to the fourth generation effects. Hence the measurements of these observables at LHC, for the above mentioned processes can serve as a good tool to investigate the indirect manifestations of the fourth generation quarks. • The same decay B → K1 (1270, 1400)l+ l− is also studied in the standard model (SM) and in universal extra dimension (UED) model. In this work we first relate the form factors through Ward identities and then express their normalization atq 2 = 0 in terms of a single constant g+ (0) which is extracted from the decays B → K1 (1270, 1400)γ. These form factors are then used to analyze the physical observables such as the branching ratio and the forward-backward asymmetry in the SM. This analysis is then extended to the UED model where the dependency of the above mentioned physical observables on the compactification radius R, the only unknown parameter in the UED model. It is shown that the zero position of the forward-backward asymmetry for the decay B → K1 (1270, 1400)μ+ μ− is sensitive to the UED model, therefore the zero position of the forward-backward asymmetry can serve as a handy tool to establish new physics predicted by the UED model. ∗ • The semileptonic Bc → Ds l+ l− (l = μ, τ ) decays have been studied in the Standard Model (SM) and in the Universal Extra Dimension (UED) model. In addition to the contribution from the Flavor Changing Neutral Current (FCNC) transitions the weak annihilation (WA) contribution is also important for this decay. It is found that the WA gives 6.7 times larger branching ratio ∗ than the penguin contribution for the decay Bc → Ds μ+ μ− . The contribution from the WA and FCNC transitions are parameterized in terms of the form factors. In this work we first relate the form factors through Ward identities and then express them in terms of g+ (0) which is extracted ∗ from the decay Bc → Ds γ through QCD sum rules approach. These form factors are then used to analyze the physical observables like branching ratio and helicity fractions of the final state ∗ Ds meson in the SM. This analysis is then extended to the UED model where the dependency of above mentioned physical observables depend on the compactification radius R. It is shown that ∗ the helicity fractions of Ds are sensitive to the UED model especially when we have muons as the final state lepton. This sensitivity is marked up at low q 2 region, irrespective of the choice of the form factors. It is hoped that in the next couple of years LHC will provide enough data on the ∗ Bc → Ds l+ l− channel, and then , these helicity fractions would serve as a useful tool to establish new physics predicted by the UED model.