Patterns of ingestion of rats during chronic oral administration of lithium chloride.

Chronic lithium administration to rodents is used to explore the potential neural mechanisms of mood stabilization, as well as to model the side effects of chronic lithium on multiple organ systems. Oral administration of lithium in the maintenance diet or drinking water is convenient, but lithium can acutely affect intake and it can mediate acquisition of conditioned taste aversions (CTA). We compared ad libitum food and fluid intake by male rats with LiCl or NaCl solutions as their sole source of fluid across 20 days, with a commonly used dosage of LiCl (24 mM: 1 g / L LiCl). To quantify the pattern of intake, rats were housed in cages equipped with lickometers to detect licks and infrared photobeams to detect food access with 6-s resolution. To determine if rats formed a CTA to LiCl, they were subsequently tested with access to NaCl. Rats showed an immediate avoidance of the LiCl solution, as seen on the first day of access by an increased latency to initiate drinking and a decreased size of drinking bouts. Rats showed a differential response to LiCl vs. NaCl after as few as 5 licks. Chronic consumption of LiCl solution led to significantly decreased food and fluid intake compared to baseline, with concomitant weight loss. The decreased intake was realized by marked changes in the pattern of drinking and feeding bouts: a decrease in per-lick volume and a decrease in licks per drinking bout, and an increase in feeding bout duration resulting in an overall decrease in eating rate. Conversely, chronic NaCl access led to an increase in drinking bout number and licks/bout. The avoidance of LiCl was likely a combination of toxic effects of ingested LiCl and rapid acquisition of a learned aversion to the taste of LiCl, as shown by an extinguishable generalized aversion to NaCl solution during subsequent NaCl test days. The marked effect of chronic oral LiCl on ingestion may impact the oral dosing of lithium as well as the rat's metabolic status.

Repeated exposure attenuates the behavioral response of rats to static high magnetic fields.

Exposure of rats to high strength static magnetic fields of 7 T or above has behavioral effects such as the induction of locomotor circling, the suppression of rearing, and the acquisition of conditioned taste aversion (CTA). To determine if habituation occurs across magnetic field exposures, rats were pre-exposed two times to a 14 T static magnetic field for 30 min on two consecutive days; on the third day, rats were given access to a novel 0.125% saccharin prior to a third 30-min exposure to the 14 T magnetic field. Compared to sham-exposed rats, pre-exposed rats showed less locomotor circling and an attenuated CTA. Rearing was suppressed in all magnet-exposed groups regardless of pre-exposure, suggesting that the suppression of rearing is more sensitive than other behavioral responses to magnet exposure. Habituation was also observed when rats underwent pre-exposures at 2-3h intervals on a single day. Components of the habituation were also long-lasting; a diminished circling response was observed when rats were exposed to magnetic field 36 days after 2 pre-exposures. To control for possible effects of unconditioned stimulus pre-exposure, rats were also tested in a similar experimental design with two injections of LiCl prior to the pairing of saccharin with a third injection of LiCl. Pre-exposure to LiCl did not attenuate the LiCl-induced CTA, suggesting that 2 pre-exposures to an unconditioned stimulus are not sufficient to explain the habituation to magnet exposure. Because the effects of magnetic field exposure are dependent on an intact vestibular apparatus, and because the vestibular system can habituate to many forms of perturbation, habituation to magnetic field exposure is consistent with mediation of magnetic field effects by the vestibular system.

Evidence for a cephalic site of action of high magnetic fields on the behavioral responses of rats.

Static high magnetic fields (MFs) from 7 T to 9 T can elicit behavioral responses in rodents such as suppression of rearing, locomotor circling, and acquisition of a conditioned taste aversion (CTA). MF exposure also induces c-Fos expression in the visceral and vestibular nuclei of the brainstem, suggesting the stimulation of some sensory pathways. It is not clear, however, if the effects of the MF are caused by exposure to the uniform maximal field at the center of the magnet, or by exposure to the steep field gradients along the bore of the magnet during the rat's placement. In addition, the site of action within the rat is unknown. In an attempt to limit MF exposure to rostral or caudal portions of the rats' body, we exposed male and female rats at different positions within the bore of a 14.1-T superconducting magnet ranging from 2 cm (1.6 T at the head) to 155 cm (0.05 T at the head), with the center of the bore at 65 cm (14.1 T across the whole body). This approach also allowed us to expose rats to the maximal field strength (14.1 T) vs. the maximal field gradients (54 T/m). To assess both immediate and delayed behavioral effects, locomotor and CTA responses were recorded. A small but significant CTA was seen after exposure of the head to the lowest MF tested (0.05 T at 155 cm). Graded effects were seen, however, with greater circling and CTA acquisition as the MF strength increased at the rostral end of the rat. This suggests a cephalic site of action. Furthermore, maximal circling and CTA were induced after exposure to the uniform center field, and not after exposure to high field gradients on either side of the center. This suggests that the behavioral responses seen after MF exposure are a consequence of the uniform static field at the center of the magnet, and are not caused by passage through, or exposure to, the vertical field gradients. Female rats responded similarly to male rats, although magnet-induced CTA appeared resistant to extinction in female rats.

Rats avoid high magnetic fields: dependence on an intact vestibular system.

High strength static magnetic fields are thought to be benign and largely undetectable by mammals. As magnetic resonance imaging (MRI) machines increase in strength, however, potential aversive effects may become clinically relevant. Here we report that rats find entry into a 14.1 T magnet aversive, and that they can detect and avoid entry into the magnet at a point where the magnetic field is 2 T or lower. Rats were trained to climb a ladder through the bore of a 14.1 T superconducting magnet. After their first climb into 14.1 T, most rats refused to re-enter the magnet or climb past the 2 T field line. This result was confirmed in a resistive magnet in which the magnetic field was varied from 1 to 14 T. Detection and avoidance required the vestibular apparatus of the inner ear, because labyrinthectomized rats readily traversed the magnet. The inner ear is a novel site for magnetic field transduction in mammals, but perturbation of the vestibular apparatus would be consistent with human reports of vertigo and nausea around high strength MRI machines.

Suppression of drinking by exposure to a high-strength static magnetic field.

High-strength static magnetic fields of 7 T and above have been shown to have both immediate and delayed effects on rodents, such as the induction of locomotor circling and the acquisition of conditioned taste aversions. In this study, the acute effects of magnet field exposure on drinking were examined. Exposure to a 14.1-T magnetic field for as little as 5 min significantly decreased the amount of a glucose and saccharin solution (G+S) consumed by water-deprived rats over 10 min. The decreased intake could be accounted for largely, but not entirely, by an increase in the latency of magnet-exposed rats to initiate drinking. When intake was measured for 10-60 min after the initiation of drinking, thus controlling for increased latency, magnet-exposed rats still consumed less G+S than sham-exposed rats. The increased latency was not due simply to an inability of magnet-exposed rats to reach the elevated sipper tube of the G+S bottle, providing rats with long tubes that could be reached without raising their heads normalized intake but latency was still increased. The increased latency and decreased intake appeared to be secondary to somatic effects of magnet exposure, however, because during intraoral infusions magnet-exposed rats consumed the same amount of G+S with the same latency to reject as sham-exposed rats. The suppression of drinking by magnetic field exposure is consistent with the acute effects of other aversive stimuli, such as whole-body rotation, on short-term ingestion. These results add to the evidence that high-static strength magnetic fields can have behavioral effects on rodents.

Behavioral effects on rats of high strength magnetic fields generated by a resistive electromagnet.

It has been reported previously that exposure to static high magnetic fields of 7 T or above in superconducting magnets has behavioral effects on rats. In particular, magnetic field exposure acutely but transiently suppressed rearing and induced walking in tight circles; the direction of circular locomotion was dependent on the rats' orientation within the magnet. Furthermore, when magnet exposure was paired with consumption of a palatable, novel solution, rats acquired a persistent taste aversion. In order to confirm these results under more controlled conditions, we exposed rats to static magnetic fields of 4 to 19.4 T in a 189 mm bore, 20 T resistive magnet. By using a resistive magnet, field strengths could be arbitrary varied from -19.4 to 19.4 T within the same bore. Rearing was suppressed after exposure to 4 T and above; circling was observed after 7 T and above. Conditioned taste aversion was acquired after 14 T and above. The effects of the magnetic fields were dependent on orientation. Exposure to +14 T induced counter-clockwise circling, while exposure to -14 T induced clockwise circling. Exposure with the rostral-caudal axis of the rat perpendicular to the magnetic field produced an attenuated behavioral response compared to exposure with the rostral-caudal axis parallel to the field. These results in a single resistive magnet confirm and extend our earlier findings using multiple superconducting magnets. They demonstrate that the behavioral effects of exposure within large magnets are dependent on the magnetic field, and not on non-magnetic properties of the machinery. Finally, the effects of exposure to 4 T are clinically relevant, as 4 T magnetic fields are commonly used in functional MRI assays.