Leading current interests of the PI include physiologically-oriented basic studies of the postnatal development and adult functional status of postsynaptic and presynaptic receptors for dopamine in mammalian brain tissue, particularly as regards the ratio of receptor subtypes (D1:D2) in brain regions, the state of functional responses of pre- and postsynaptic receptors to selective D1 and D2 agonists and antagonists, and the status of molecular components of """"""""effector"""""""" mechanisms mediating the actions of dopaminergic receptors. A specific problem is to develop improved probes of putative dopaminergic autoreceptors proposed as a critical control mechanisms for dopamine synthesis and release, following current leads developed with non-catechol analogs of dopamine, including monohydroxyaporphines. Another specific theme involves applying known and unique partial receptor agonists or mixed agonist-antagonists to the problem of developing improved antipsychotic, mood-altering, or antiaddictive agents with reduced risks of acute and late neurological side effects or of other adaptive responses almost universally characteristic of available psychotropic drugs. Related work that complements searches for new pharmacotherapeutic principles involves clarification of selected aspects of the neuropharmacology of clinically available antipsychotic agents, including: more realistic appraisals of the timecourse of actions of neuroleptics than have been provided to date, pursuit of the PI's observation that sensitivity to neuroleptics in the developing rat decreases by as much as 75-fold during maturation, broader assessments of effects of long-term neuroleptic treatment on tissue levels and functions of catecholamine (adrenergic as well as dopaminergic) receptors in mammalian brain tissue, and consideration of possible pharmacologic means of avoiding unwanted effects of psychotropic agents on such receptors that may contribute to tolerance (loss of efficacy) or to late side effects (such as dyskinsias).
| Joffe, Hadine; Hall, Janet E; Cohen, Lee S et al. (2003) A putative relationship between valproic acid and polycystic ovarian syndrome: implications for treatment of women with seizure and bipolar disorders. Harv Rev Psychiatry 11:99-108 |
