This study investigated whether environmental enrichment (EE) could overcome the context dependency of cocaine-cue extinction learning to prevent relapse. Rats underwent cocaine self-administration training and extinction in different contexts with or without EE. Results showed that EE facilitated the rate of extinction learning regardless of context change. However, combining EE with extinction in the same drug context prevented cocaine relapse, while EE paired with extinction in a novel context did not prevent immediate relapse. Thus, EE cannot overcome the context dependency of extinction learning on its own.
Ketogenic Diet Plus Hyperbaric Oxygen Therapy in Treating Cancer Dominic D'Agostino
A University of South Florida (USF) associate professor, Dominic D’Agostino, PhD, maintains a research focus on metabolic therapies for epilepsy, seizures, brain cancer, and other conditions. Dr. Dominic D’Agostino’s present focus is on the ketogenic diet and ketone esters, and their neuroprotective and anticonvulsant effects.
Ketogenic Diet Plus Hyperbaric Oxygen Therapy in Treating Cancer Dominic D'Agostino
A University of South Florida (USF) associate professor, Dominic D’Agostino, PhD, maintains a research focus on metabolic therapies for epilepsy, seizures, brain cancer, and other conditions. Dr. Dominic D’Agostino’s present focus is on the ketogenic diet and ketone esters, and their neuroprotective and anticonvulsant effects.
Short-Term Effects of Repeated Olfactory Administration of Homeopathic Sulphu...Francisco Navarro
Short-Term Effects of Repeated Olfactory Administration of
Homeopathic Sulphur or Pulsatilla on Electroencephalographic
Alpha Power in Healthy Young Adults
Examining Neurobehavioral Toxicity of Patulin in Adult ZebrafishQuang Nguyen
The content of this PowerPoint is strictly for the purpose of submission to the Sigma Xi Research Showcase. Please do not quote/cite/reference materials in this file in its entirety. I am not responsible for any misrepresentation of its reproduction. Any reproduction must have the author's written approval.
Otherwise, I hope you enjoy the slides.
Check out my page at http://patulinzebrafish.tumblr.com/
The IOSR Journal of Pharmacy (IOSRPHR) is an open access online & offline peer reviewed international journal, which publishes innovative research papers, reviews, mini-reviews, short communications and notes dealing with Pharmaceutical Sciences( Pharmaceutical Technology, Pharmaceutics, Biopharmaceutics, Pharmacokinetics, Pharmaceutical/Medicinal Chemistry, Computational Chemistry and Molecular Drug Design, Pharmacognosy & Phytochemistry, Pharmacology, Pharmaceutical Analysis, Pharmacy Practice, Clinical and Hospital Pharmacy, Cell Biology, Genomics and Proteomics, Pharmacogenomics, Bioinformatics and Biotechnology of Pharmaceutical Interest........more details on Aim & Scope).
A Study on the Toxic Effect of Different Doses of Diclofenac Sodium on the De...Prof. Hesham N. Mustafa
SUMMARY: The toxic effects of different doses of diclofenac sodium (DS) on the kidney on the postnatal period (0-7 days) by
morphometrical and immunohistochemical methods were investigated. For this purpose, 15 female adult wistar albino rats were used and
divided into 5 main groups. Group Ia served as normal control, physiologic group Ib received normal saline, group II received low dose (3.9
mg/kg), group III received medium dose (9 mg/kg) and group IV received high dose (18 mg/kg). Male offspring’s from 0-7 days after birth
were used in this study. On the 8th day of postnatal life, all animals were anesthetized. Then, the kidney samples were analyzed. Haematoxylin
and eosin staining showed degeneration and necrosis, apparent atrophy of the glomeruli, mononuclear cell infiltration, congested vessels,
increased fibrous tissue and distortion of the proximal convoluted tubules with interruption of the brush margin of the DS treated group.
Increased level of Caspase-3 and upregulation of TNF-α with different doses of DS. In light of our findings, DS may lead to adverse effects
that are dose-dependent in the prenatal subjected kidney to this drug.
KEY WORDS: Diclofenac sodium; Proximal convoluted tubules; Apoptosis;Cyclooxygenase.
A study on the toxic effect of different doses of Diclofenac sodium on the de...Prof. Hesham N. Mustafa
The toxic effects of different doses of diclofenac sodium (DS) on the kidney on the postnatal period (0-7 days) by morphometrical and immunohistochemical methods were investigated. For this purpose, 15 female adult wistar albino rats were used and divided into 5 main groups. Group Ia served as normal control, physiologic group Ib received normal saline, group II received low dose (3.9 mg/kg), group III received medium dose (9 mg/kg) and group IV received high dose (18 mg/kg). Male offspring’s from 0-7 days after birth were used in this study. On the 8th day of postnatal life, all animals were anesthetized. Then, the kidney samples were analyzed. Haematoxylin and eosin staining showed degeneration and necrosis, apparent atrophy of the glomeruli, mononuclear cell infiltration, congested vessels, increased fibrous tissue and distortion of the proximal convoluted tubules with interruption of the brush margin of the DS treated group. Increased level of Caspase-3 and upregulation of TNF-α with different doses of DS. In light of our findings, DS may lead to adverse effects that are dose-dependent in the prenatal subjected kidney to this drug.
Keywords : Diclofenac sodium; Proximal convoluted tubules; Apoptosis; Cyclooxygenase.
Short-Term Effects of Repeated Olfactory Administration of Homeopathic Sulphu...Francisco Navarro
Short-Term Effects of Repeated Olfactory Administration of
Homeopathic Sulphur or Pulsatilla on Electroencephalographic
Alpha Power in Healthy Young Adults
Examining Neurobehavioral Toxicity of Patulin in Adult ZebrafishQuang Nguyen
The content of this PowerPoint is strictly for the purpose of submission to the Sigma Xi Research Showcase. Please do not quote/cite/reference materials in this file in its entirety. I am not responsible for any misrepresentation of its reproduction. Any reproduction must have the author's written approval.
Otherwise, I hope you enjoy the slides.
Check out my page at http://patulinzebrafish.tumblr.com/
The IOSR Journal of Pharmacy (IOSRPHR) is an open access online & offline peer reviewed international journal, which publishes innovative research papers, reviews, mini-reviews, short communications and notes dealing with Pharmaceutical Sciences( Pharmaceutical Technology, Pharmaceutics, Biopharmaceutics, Pharmacokinetics, Pharmaceutical/Medicinal Chemistry, Computational Chemistry and Molecular Drug Design, Pharmacognosy & Phytochemistry, Pharmacology, Pharmaceutical Analysis, Pharmacy Practice, Clinical and Hospital Pharmacy, Cell Biology, Genomics and Proteomics, Pharmacogenomics, Bioinformatics and Biotechnology of Pharmaceutical Interest........more details on Aim & Scope).
A Study on the Toxic Effect of Different Doses of Diclofenac Sodium on the De...Prof. Hesham N. Mustafa
SUMMARY: The toxic effects of different doses of diclofenac sodium (DS) on the kidney on the postnatal period (0-7 days) by
morphometrical and immunohistochemical methods were investigated. For this purpose, 15 female adult wistar albino rats were used and
divided into 5 main groups. Group Ia served as normal control, physiologic group Ib received normal saline, group II received low dose (3.9
mg/kg), group III received medium dose (9 mg/kg) and group IV received high dose (18 mg/kg). Male offspring’s from 0-7 days after birth
were used in this study. On the 8th day of postnatal life, all animals were anesthetized. Then, the kidney samples were analyzed. Haematoxylin
and eosin staining showed degeneration and necrosis, apparent atrophy of the glomeruli, mononuclear cell infiltration, congested vessels,
increased fibrous tissue and distortion of the proximal convoluted tubules with interruption of the brush margin of the DS treated group.
Increased level of Caspase-3 and upregulation of TNF-α with different doses of DS. In light of our findings, DS may lead to adverse effects
that are dose-dependent in the prenatal subjected kidney to this drug.
KEY WORDS: Diclofenac sodium; Proximal convoluted tubules; Apoptosis;Cyclooxygenase.
A study on the toxic effect of different doses of Diclofenac sodium on the de...Prof. Hesham N. Mustafa
The toxic effects of different doses of diclofenac sodium (DS) on the kidney on the postnatal period (0-7 days) by morphometrical and immunohistochemical methods were investigated. For this purpose, 15 female adult wistar albino rats were used and divided into 5 main groups. Group Ia served as normal control, physiologic group Ib received normal saline, group II received low dose (3.9 mg/kg), group III received medium dose (9 mg/kg) and group IV received high dose (18 mg/kg). Male offspring’s from 0-7 days after birth were used in this study. On the 8th day of postnatal life, all animals were anesthetized. Then, the kidney samples were analyzed. Haematoxylin and eosin staining showed degeneration and necrosis, apparent atrophy of the glomeruli, mononuclear cell infiltration, congested vessels, increased fibrous tissue and distortion of the proximal convoluted tubules with interruption of the brush margin of the DS treated group. Increased level of Caspase-3 and upregulation of TNF-α with different doses of DS. In light of our findings, DS may lead to adverse effects that are dose-dependent in the prenatal subjected kidney to this drug.
Keywords : Diclofenac sodium; Proximal convoluted tubules; Apoptosis; Cyclooxygenase.
1. Effects of Environmental Enrichment on the Context Dependency
of Cocaine-Cue Extinction Learning for Relapse Prevention
• Cocaine addiction currently has no effective treatment
methods.
• Drug cue-extinction (exposure therapy) has been
proposed as a potential treatment method, but has
shown to be context dependent (Conklin & Tiffany et al 2002).
• To be of use in clinical settings, this treatment method
would need to be effective in a novel context.
• Previous studies show that context dependency of
extinction learning is overcome with administration of a
cognitive enhancing drug (e.g. DCS) (Torregrossa et al 2010).
• EE is equally effective as a cognitive enhancing drug
when brief interventions of EE are paired with cocaine-
cue extinction training (Gauthier et al 2015).
• EE enhances neurogenesis and cognitive functioning,
which in turn facilitates learning (Beauquis et al 2010; Fan et al
2007; Gauthier et al 2015).
• The context dependency of extinction learning may be
overcome if it is paired with EE.
• What effects does EE have on extinction learning and
relapse when extinction is given in a novel context?
• Beauquis, J., Roig, P., De Nicola, A. F., & Saravia, F. (2010). Short-Term
Environmental Enrichment Enhances Adult Neurogenesis, Vascular Network and
Dendritic Complexity in the Hippocampus of Type 1 Diabetic Mice. PLoS ONE,
5(11), e13993.
• Conklin CA, Tiffany ST. (2002). Applying extinction research and theory to cue-
exposure addiction treatments. Addiction, 97:155–167.
• Fan, Y., Liu, Z., Weinstein, P. R., Fike, J. R. and Liu, J. (2007), Environmental
enrichment enhances neurogenesis and improves functional outcome after cranial
irradiation. European Journal of Neuroscience, 25: 38–46.
• Gauthier, J. M., Lin, A., Nic Dhonnchadha, B. Á., Spealman, R. D., Man, H.-Y., and
Kantak, K. M. (2015) Environmental enrichment facilitates cocaine-cue extinction,
deters reacquisition of cocaine self-administration and alters AMPAR GluA1
expression and phosphorylation. Addiction Biology.
• Torregrossa, M. M., Sanchez, H., & Taylor, J. R. (2010). D-cycloserine Reduces the
Context- Specificity of Pavlovian Extinction of Cocaine Cues Through Actions in the
Nucleus Accumbens. The Journal of Neuroscience, 30(31), 10526–10533.
METHODS
• Cocaine self-administration
(0.3mg/kg) under a Second-
Order Schedule
• Adult Male Wistar rats, group
sizes varied n = 8-12
• Rats were placed into 1 of 3
groups:
• Group 1: Rats received EXT in
same drug context (A) with
no EE (control group)
• Group 2: Rats received EXT in
same drug context (A) with EE
• Group 3: Rats received EXT in
novel context (B) with EE
INTRODUCTION
RESEARCH QUESTION
During baseline self-administration (before treatments), there were no preexisting group differences
• One way ANOVAs confirmed this for average active (p=0.072) and inactive (p=0.28) lever responses,
and cocaine infusions (p=0.21).
• One outlier rat (†) disproportionately represented the ABA + EE group for inactive lever responses;
removing the outlier resulted in a more accurate representation of the group.
EE facilitated extinction learning
• During extinction (no cocaine delivery), lever pressing
generally decreased across weekly sessions.
• A two-way RM ANOVA showed a main effect of group
(F[2,25] = 4.1, p=0.030). Tukey tests show that the
rats receiving extinction in context A with EE
responded significantly less than the control group
(^ p=0.04).
• Dunnett tests showed that rats receiving EE had
significantly less responding than the control group
on extinction session 2, regardless if they received
extinction in context A or B (* p < 0.01).
RESULTS (CONT.)
EE deterred relapse after extinction in context A
• Repeated two-way ANOVA showed that there is
a main effect of group (F[2,25] = 7.61, p=0.003).
• Tukey tests showed that rats receiving extinction
in context A with EE responded significantly less
during reacquisition compared to rats receiving
extinction in novel context B with EE (^ p=0.002)
• Dunnett post-hoc tests showed that rats
receiving extinction in context A with EE
deterred cocaine relapse for up to 12 sessions
compared to the control group (* p<0.05).
CITATIONS
CONCLUSIONS
Presented by:
Kyle Mabry
• EE facilitated the rate of extinction learning, regardless of the change in context.
• Combining EE with extinction learning in context A deterred relapse to baseline
rates of cocaine self-administration.
• When EE was paired with extinction learning in context B, however, rats relapsed
immediately, as also observed in the control group.
• This suggests that EE is not able to overcome the context dependency of extinction
learning.
• Pairing EE with a cognitive enhancing drug may be able to surmount the context
dependency of extinction learning.
OR
Aspen bedding Aspen beddingAspen bedding Cedar bedding
= Intermittent tone
Black wall
Cedar bedding
= White noise
Clear wall
Aspen bedding
ABSTRACT
Addiction is marked by repeated cycles of abstinence followed by drug relapse
brought on by re-exposure to drug-paired cues. Extinction learning disassociates
drug-paired cues from the drug itself, but is context-dependent. We used
environmental enrichment (EE) paired with cocaine-cue extinction training to
investigate whether EE can overcome the context dependency of extinction
learning. Adult male rats were conditioned under a second-order schedule of
cocaine delivery and cue presentation. After establishing baseline rates of
cocaine self-administration, saline was substituted for cocaine during three
weekly extinction sessions. The first group (control group) was conditioned,
extinguished and tested for relapse in the same context (AAA design), but did
not receive EE. The second group was treated identically (AAA design), but also
received EE during extinction. The third group was conditioned and relapse
tested in context A, but extinguished with EE in a novel context (ABA design). EE
consisted of two 4-hr periods provided 24 hours before and immediately
following each weekly extinction session. One week later, cocaine was again
available for 15 daily self-administration sessions to study relapse in context A.
Results showed that EE facilitated rates of extinction learning, whether
conducted in context A or context B. As previously observed, combining EE with
extinction in context A inhibited cocaine relapse. However, when EE was
combined with extinction in context B, rats relapsed immediately, as observed
in the control group. Thus, EE cannot overcome the context dependency of
extinction learning. Adjunct drug therapies may be required to surmount this
obstacle in clinical settings.
RESULTS
†
PI: Kathleen M. Kantak
GS: Jamie Gauthier
EE was provided in 4-hr
blocks 24 hours before
and immediately after
each weekly extinction
session.
Baseline Cocaine Self-Administration
A B
A
B
Editor's Notes
Individual slides for each section. (Use the correct slide size)