Robert J. Carey

Unimpaired maintenance of a conditioned avoidance response in the rat with diabetes insipidus

Abstract The ability to maintain a conditioned avoidance response (CAR) was studied in normal Long-Evans rats and rats of the Brattleboro strain which were either homozygous or heterozygous for hereditary hypothalamic diabetes insipidus (DI). Homozygous DI rats had a lower CAR acquisition rate than did normal or heterozygous DI rats. However, the homozygous DI rats exhibited significantly greater CAR retention than did the other animals over the total period of extinction testing. The greater CAR retention could not be accounted for by either increased sensitivity to the electric foot shock used as the unconditioned stimulus or by perching on the metal center barrier of the training shuttle box, a form of behavior unique to the homozygous DI rats. Since the homozygous DI rat is totally lacking in hypothalamic antidiuretic hormone (ADH), the greater CAR retention of these animals indicates that ADH is not a requirement for CAR retention.

A retracting wire knife for stereotaxic brain surgery made from a microliter syringe

Abstract A simple and reliable retracting wire knife for stereotaxic brain surgery can be constructed in literally a few minutes. A commercially available syringe is modified using only a pair of pliers and a sanding disc.

Treatment schedule as a determinant of the development of tolerance to haloperidol

Three groups of rats received haloperidol 0.5 mg/kg IP twice daily for 20 days, twice daily for 10 days, or every other day for 40 days. The rats in control groups received saline injections according to the same schedules as the experimental groups. During the chronic treatments, spontaneous motor activity was measured as an indicator of behavioral tolerance, and at the completion of treatments, limbic and striatal homovanillic acid (HVA) levels were determined in order to provide a biochemical indication of tolerance. Both of the haloperidol groups on twice-daily injection schedules exhibited a trend towards recovery of spontaneous motor activity during treatment, indicative of behavioral tolerance, as well as reduced HVA levels indicative of near complete biochemical tolerance. The group receiving haloperidol every other day exhibited a trend toward behavioral intolerance to haloperidol, along with elevated HVA levels that indicated a complete absence of tolerance. The suggested importance of treatment schedule rather than cumulative drug dosage in the development of tolerance to haloperidol may have significance to long-term side effects of chronic neuroleptic treatment such as tardive dyskinesia and clinical issues such as drug holidays.

Behavioral differences between vasopressin-deficient (Brattleboro) and normal long-Evans rats

Behavioral comparisons were made between rats of the Brattleboro strain with hereditary hypothalamic diabetes insipidus (DI) and normal Long-Evans rats. Measurements were made of activity behavior in a lighted open field and in a darkened activity chamber. Subtle measurement specific differences in the activity behavior of DI rats were found which suggested altered emotion, motivation and/or attention in the DI rats. In terms of learned behavior, DI and normal rats displayed a similar degree of habituation to all within-session activity measures in both the open field and darkened activity chamber. In a passive avoidance test, DI rats exhibited a degree of avoidance behavior equivalent to that of normal animals. Thus, these studies provide evidence that the vasopressin-deficient rat is not defective in learning and memory processes. The data can be interpreted as suggesting that vasopressin may influence memory tasks by extrinsic modulation of related states of emotionality, motivation and/or attention rather than by direct involvement in the retrieval and consolidation of information.

Altered emotionality of the vasopressin-deficient Brattleboro rat ☆

Observation of open field behavior of vasopressin-deficient (DI) and normal Long-Evans rats indicated elevated levels of open field activity for the DI rats. Exposure to an acoustic stressor resulted in decreased activity in both groups of animals but with a lesser effect on the DI rat. Handling prior to experimentation diminished the differences between DI and normal rats. Although both groups displayed an equivalent rise in plasma corticosterone in response to the open field, the addition of the acoustic stressor resulted in greater elevation of corticosterone in the normal animals. The behavioral and hormonal data suggest that the DI rat exhibits decreased emotional reactivity. Measurement of brain neurotransmitter levels revealed higher concentrations of serotonin, norepinephrine and dopamine in the limbic regions of the DI rat. These alterations may underlie the behavior reflecting decreased emotionality of the DI rat. In turn, the altered emotional state may be the basis for alteration in performance on learning/memory tasks of these animals. Thus, vasopressin effects on the retrieval and/or consolidation of information may not be direct but rather through its ability to influence the emotional state of the animal.

Relationship of changes in spontaneous motor activity to spontaneous circling in rats with unilateral 6-hydroxydopamine lesions of the substantia nigra

Two unilateral injections of 6-hydroxydopamine into the substantia nigra and ventral tegmental area of adult rats pretreated with desmethylimipramine produced severe unilateral depletions of limbic and striatal dopamine. These animals sustained global deficits in spontaneous motor activity with no recovery evident from 1 to 14 weeks postoperative. The frequency of spontaneous circling increased during the 1st few weeks postoperative and then remained stable during the last 2 months of observation. The changes in circling were independent of changes in global spontaneous motor behaviors. Biochemical determinations indicated an increased dopamine turnover in residual limbic and striatal dopamine neurons but with substantially changed dihydroxyphenylacetic acid:homovanillic acid ratios. The absence of functional recovery of both normal and asymmetric motoric behavior indicates that severe uncompensated deficits in motoric function produced by unilateral 6-hydroxydopamine lesions can provide a useful animal model for the study of dopaminergic contributions to movement disorders.

Effect of vasopressin on open field and activity behavior of the vasopressin-deficient (Brattleboro) rat

The effect of 1 and 5 micrograms AVP injections on open field and photoactivity chamber behavior of D.I. and normal Long-Evans animals was studied. Administration of 5 micrograms AVP (SC) resulted in a statistically significant depression of both open field and photochamber activity in the D.I. rat, but had a less pronounced effect on normal animals. However, 1 microgram AVP resulted in only minor alterations of activity in both D.I. and normal animals. In terms of learned behavior, D.I. and normal animals displayed similar within-session habituation when comparisons were made following the same treatment conditions. Thus, this study supports the hypothesis that vasopressin may influence memory tasks by modulation of related states of emotionality, motivation, and/or attention rather than by direct involvement in the retrieval and/or consolidation of information.

Ethanol drinking elicited during electrical stimulation of the lateral hypothalamus.

Abstract The fact that rats will drink intoxicating amounts of aversive ethyl alcohol solutions during electrical stimulation of the lateral hypothalamus in a standard test chamber was demonstrated. The ingestion of ethanol was produced rapidly and daily for as long as 25 days without any obvious deleterious effects. Possible applications to the development of an animal model for the study of alcoholism are discussed.

A comparison of the food intake suppression produced by giving amphetamine as an aversion treatment versus as an anorexic treatment.

Separate groups of rats were given either 1 or 2 mg/kg injections of amphetamine 30 min before or after eating a preferred high-fat food. When given before eating as an anorexic treatment, amphetamine initially suppressed intake almost completely, but with repeated injections tolerance developed. In contrast, amphetamine given after eating as an aversion treatment initially had little effect on intake, but with repeated injections it suppressed intake almost completely in rats receiving the higher dose.

Facilitation of responding for rewarding brain stimulation by a high dose of amphetamine when hyperthermia is prevented

Rats given a 5 mg/kg injection of d-amphetamine did not respond for brain stimulation reward when tested under normal laboratory temperatures. In addition to the usual manifestations of stereotypy the rats were markedly hyperthermic. If the hyperthermia was prevented, however, by initially placing the rats in a cold room (10°C) and subsequently testing for brain stimulation under a cool chamber temperature (14–16°C), the rats responding for brain stimulation was facilitated. Thus, the occurrence of hyperthermia appears to be a critical factor responsible for this behavioral dysfunction produced by a high dose of amphetamine.