Oral self-administration of ethanol and cocaine in rats.

Most laboratory animal studies on self-administration of drugs of abuse use only one drug, whereas humans frequently engage in polydrug use. For this reason, we studied oral self-administration of ethanol (E) and cocaine (C) with the free choice bottle method using a single drug alone, a combination (E and C in separate bottles) or a mixture of both drugs in a single bottle. Young female rats (45 days) consumed similar amounts of C if offered alone (12.4 +/- 7.5 mg/kg/day), in the presence of ethanol (10.6 +/- 3.5) or as E/C mixture (8.0 +/- 4.0). They also consumed similar amounts of E if offered alone (3.8 +/- 1.6 ml/kg/day), in the presence of C (2.3 +/- 0.8) or E/C mixture (2.4 +/- 1.1). Voluntary consumption of both drugs varied markedly among animals but was consistent in a given rat. No correlation occurred between consumption of E and C. Young male rats behaved similarly and consumed similar amounts of E and C alone, in combination and as mixture. While E consumption was similar, C consumption was higher in female rats. Old male rats (180 days) were similar to young male rats. The presence of a saccharin solution as a distracter had no effect on intake of E or C in young females but reduced E intake only in young male rats. In young animals, prior voluntary consumption of either E or C had no effect on subsequent voluntary consumption of the same or other drug offered in combination. These results indicate that this model may be useful to study polydrug use in humans, that consumption of both E and C is strongly controlled by an individual animal, that prior exposure to one drug had no or little effect on a subsequent consumption of the same or other drug in combination and that intake of E or C seems to be independent of each other suggesting two independent reward centers.

Application of spin-echo nuclear magnetic resonance to whole-cell systems. Membrane transport.

A new method for studying membrane transport is presented. High resolution n.m.r. is used to measure the distribution of small molecules between the intracellular and extracellular compartments. The method uses spin-echo techniques and relies on a difference in the magnetic susceptibility of the media inside and outside of cells. It also provides simultaneous information on the metabolic status of the cell. The method is illustrated by a study of alanine and lactate transport in the human erythrocyte.

Structural studies on lamellated osmiophilic bodies isolated from pig lung. 31P NMR results and water content.

1. Lamellated osmiophilic bodies are intracellular organelles in which pulmonary surfactant is stored prior to secretion. They contain about 85% phospholipid (per dry weight) and dipalmitoyl phosphatidylcholine is a major constituent, and although their ultrastructure is uncertain it is generally supposed that they resemble liposomes. However, liposomes are stable because layers of water are interposed between the lipid bilayers whereas an essential aspect of the function of lamellated bodies is that, subsequent to their secretion, they are rapidly disrupted to form a surface-active film which covers the respiratory epithelium of the lung. 2. A new method for isolating lamellated bodies from pig lung is described which has the advantage of speed and simplicity and which results in increased yields. The homogeneity of the preparation is similar to that obtained by other methods. 3. 31P NMR spectra of lamellated bodies showed that at 40 degrees C about 95% of the phospholipid was present as extended bilayers and that about 5% was present in a phase exhibiting isotropic head group mobility (tau R less than 10(-5) s). It is suggested that this phase may be due to apolar proteins which are present both in lamellated bodies and in liposomes prepared from lipids extracted from them. 4. The internal water content of lamellated bodies has been measured gravimetrically and the hydration of the phospholipid head groups has been examined by 31P NMR. The two methods gave results in good agreement and show that there are about seven molecules of water/molecule of phospholipid. It is concluded that although the phospholipid head groups in lamellated bodies are fully hydrated, there is no zone of free water. 5. Lamellated bodies are osmotically insensitive to NaCl whereas liposomes prepared from lipids extracted from them behave like perfect osmometers. It is suggested that the osmotic insensitivity and restricted water content of lamellated bodies are important to their function and dependent upon polar proteins in the outer limiting membrane.

The adsorption of divalent cations to phosphatidylcholine bilayer membranes.

Electrophoretic mobility and 31P NMR measurements were combined to test whether the combination of the Henry, Boltzmann and Grahame equations is capable of describing the adsorption of divalent cations of phosphatidylcholine membranes. Cobalt was chosen for this study because, of all the common divalent cations, its effects on the 31P NMR spectrum of phosphatidylcholine membranes are easiest to interpret. Both the 31P NMR data on the adsorption of cobalt and the zeta potential data calculated from the electrophoretic mobility in the presence of cobalt are well described by the combination of these three equations. Electrophoretic mobility measurements were also performed with a number of other divalent cations and the zeta potentials were, in all cases, well described by the combination of these three equations. The binding deduced from such measurements decreases in the sequence: Mn2+, Mg2+, Ca2+, Co2+, Ni2+, Sr2+, Ba2+. If we assume that a lipid molecule occupies an area of 60 A2 and that there is a 1 : 1 stoichiometry for the binding of the divalent ions to phosphatidylcholine, the dissociation constants are, respectively: 0.3, 1.0, 1.0, 1.2, 1.2, 2.8, 3.6 M.