ABSTRACT
The effects of dietary glucose (chow containing 0%, 10%, 20%, or 40% glucose, w/w) on chronic haloperidol-induced changes in dopamine (DA) neuronal activity were tested. Rats were treated daily by oral gavage for 21 days with either water or 0.5 mg/kg haloperidol, then anesthetized for in vivo electrophysiological recording. The numbers of spontaneously active DA neurons in the substantia nigra (A9) and ventral tegmental area (A10) regions of the midbrain were estimated with the cells-per-track sampling method. In rats fed standard chow, haloperidol significantly reduced the number of active neurons in both regions compared to water controls. In water controls there were no differences in DA cells per track between rats fed standard chow or chow containing 10% or 20% glucose, whereas these glucose diets significantly attenuated the effects of chronic haloperidol on DA cells per track. The 40% glucose diet itself nonsignificantly reduced cells per track and, in turn, nonsignificantly attenuated the effects of haloperidol. The results demonstrate that dietary glucose content can alter haloperidol-induced changes in the activity of midbrain DA neurons.
Subject(s)
Antipsychotic Agents/pharmacology , Diet , Glucose/pharmacology , Haloperidol/pharmacology , Neurons/drug effects , Action Potentials/drug effects , Action Potentials/physiology , Animals , Body Weight , Dopamine/metabolism , Eating , Electrophysiology , Male , Mesencephalon/drug effects , Mesencephalon/physiology , Microelectrodes , Neurons/physiology , Rats , Rats, Sprague-DawleyABSTRACT
Mutant 5-hydroxytryptamine (5-HT)3A receptors, in which changes were made at Ile294, position 16', of the second transmembrane domain, were assessed for alterations in macroscopic response kinetics and modulation by alcohols. Function of heterologously expressed receptors was measured in Xenopus oocytes in the two-electrode voltage clamp configuration and in human embryonic kidney 293 cells using whole cell patch-clamp electrophysiological recordings with rapid drug application. Compared with the wild-type receptor, a decrease in the 5-HT EC50 value in the Ile294Thr mutant was observed, whereas an increase in the 5-HT EC50 value in the Ile294Leu mutant was measured. Ile294Thr receptors showed a marked reduction in the extent of desensitization. Ethanol and 2,2,2-trichloroethanol (TCEt) enhanced 5-HT-mediated currents in wild-type and Ile294Leu receptors, but inhibited or had little stimulatory effect in the Ile294Thr mutant. Kinetic analysis revealed that in the presence of TCEt, the slope of activation was unchanged in the Ile294Thr mutant and increased in the wild-type receptor. Alcohol cutoff was altered with wild-type = heptanol and Ile294Leu = hexanol. Kinetic changes in the Ile294Thr mutant that favor the open channel state, as well as reduction in the rate of channel activation in the presence of TCEt, likely underlie this mutant's altered response to n-chain alcohols.
Subject(s)
Ethanol/pharmacology , Receptors, Serotonin/metabolism , Serotonin/metabolism , Cells, Cultured , Electrophysiology , Humans , Membrane Proteins/genetics , Membrane Proteins/metabolism , Mutagenesis, Site-Directed , Patch-Clamp Techniques , Protein Structure, Tertiary/genetics , Receptors, Serotonin/drug effects , Receptors, Serotonin/genetics , Receptors, Serotonin, 5-HT3ABSTRACT
Peripheral administration of adenosine A(1) receptor selective agonists is generally thought to protect the hippocampus against ischemic damage via central actions. We examined the effects of two peripherally administered A(1) agonists, cyclohexyladenosine (CHA) and adenosine amine congener (ADAC), on synaptic transmission in the hippocampus and on indices of cardiovascular function. We conclude that the permeability of these agonists is not sufficient to result in concentrations necessary to activate central adenosine A(1) receptors within the hippocampus.
