The Division of Molecular Neuropsychopharmacology provides the following graduate level courses:
• Pharmacology (Psychopharmacology/Neuropharmacology) 824, Spring Quarter, Co-Directed by Dr. Maria H. Neff and Dr. Norton H. Neff; 30 hr, 3 credits.
• Fundamentals of Grant Writing; IBGP 707, Autumn Quarter, Co-Directed by Dr. Maria H. Neff and Dr. Norton H. Neff; team taught; 20 hr, 2 credits, 6 lectures.
• Fundamentals of Grant Writing; IBGP 708, Spring Quarter, Directed and lectured by Dr. Maria H. Neff, 30 hr, 2 credits
We are continuing our research projects on nicotine addiction and the signaling of GM1 via the GDNF receptor complex. Effort was focused on completing studies, analyzing data and publishing manuscripts. Our work with nicotine addiction has shown:
1) That the function of dopamine transporter is increased early during nicotine withdrawal in a mouse model of nicotine abstinence. This finding provides a molecular rationale for the use of dopamine uptake blockers, such a Bupoprion, in the treatment of nicotine withdrawal, and assigns a role for the dopamine transport in the dopaminergic deficits seen in nucleus accumbens, which are thought to be responsible for the negative affect associated with nicotine withdrawal.
2) That the VMAT2 is up-regulated in the striatum of nicotine withdrawn mice, suggesting a coordinated response of membrane transporters to maintain dopaminergic neurotransmission.
3) That the kappa opioid receptors are desensitized early during nicotine withdrawal, suggesting an adaptive response to reduce dysphoria. The paper with the data was recognized by the F1000 Biology as “Must Read” for its originality and translational implications for nicotine addiction.
4) That delta opioid receptors are desensitized in the shell of nucleus accumbens during early nicotine withdrawal, suggesting an opioid role in the emotional responses, anhedonia and anxiety, associated with nicotine withdrawal. Our work suggests that delta opioid agonists have the potential to improve negative affect at certain times during the nicotine addiction cycle.
5) Our work with the GM1 signaling though the GDNF receptor complex provided evidence that GM1 induces activation/phosphorylation of Ret receptor tyrosine kinase in striatal slices in situ by apparently enhancing the binding of the endogenous ligand GDNF on GFRα1 receptor. The data suggest that GM1 is a GDNF mimetic, and, in part, explain the neurorestorative effects of GM1 in animal models of Parkinson’s Disease as well as in patients with Parkinson’s Disease.