Pharmacy and Pharmaceutical Sciences Commons^™

Point Substitutions In G Protein-Coupled Receptors, Jessica Brown

Undergraduate Student Research Internships Conference

G protein-coupled receptors (GPCRs) are proteins that are important in physiological regulatory processes within the body, and for this reason are important drug targets. When bound to an agonist, such as neurotransmitters or hormones, the receptor adopts an active state to allow these biochemical pathways to occur. However, mutations can arise within the receptor that affect its ability to bind its agonist. This natural variation found within the genome can make it difficult to design pharmaceuticals to target the receptors.

To see the effects of these point substitutions on agonist-induced receptor activation, mutations were made within a negative allosteric site …

Positive Allosteric Modulator Of Gabab Receptor Alters Behavioral Effects But Not Afterdischarge Progression Induced By Partial Hippocampal Kindling., L Stan Leung, Miao Jin, Liangwei Chu, Jingyi Ma

Physiology and Pharmacology Publications

Hippocampal seizures decreased the function of GABAB receptors, which may further increase seizure susceptibility and contribute to development of schizophrenia-like behaviors. Recent literature indicates that GABAB receptor agonist may normalize schizophrenia-like behaviors and prevent drug-induced behavioral sensitization. We hypothesized that positive modulation of GABAB receptor function during seizure induction will reduce seizure-induced schizophrenia-like behaviors. Using a partial hippocampal kindling model, afterdischarges were induced after injection of saline or dimethyl sulfoxide (vehicle-kindled rats), or a GABAB receptor positive allosteric modulator CGP7930, at 1 mg/kg i.p. (CGP1-kindled) or 5 mg/kg i.p. (CGP5-kindled). The increase in the primary afterdischarge duration during kindling was …

Septohippocampal Gabaergic Neurons Mediate The Altered Behaviors Induced By N-Methyl-D-Aspartate Receptor Antagonists., Jingyi Ma, Siew Kian Tai, L Stan Leung

Physiology and Pharmacology Publications

We hypothesize that selective lesion of the septohippocampal GABAergic neurons suppresses the altered behaviors induced by an N-methyl-D-aspartate (NMDA) receptor antagonist, ketamine or MK-801. In addition, we hypothesize that septohippocampal GABAergic neurons generate an atropine-resistant theta rhythm that coexists with an atropine-sensitive theta rhythm in the hippocampus. Infusion of orexin-saporin (ore-SAP) into the medial septal area decreased parvalbumin-immunoreactive (GABAergic) neurons by ~80%, without significantly affecting choline-acetyltransferase-immunoreactive (cholinergic) neurons. The theta rhythm during walking, or the immobility-associated theta induced by pilocarpine, was not different between ore-SAP and sham-lesion rats. Walking theta was, however, more disrupted by atropine sulfate in ore-SAP than …