Engineering topics
Publications and source records attributed to Crampton, George H..
The topics covered include the following: the emetic stimuli used on the cats in the study; analysis of the constituents of the cerebral spinal fluid (CSF) during motion sickness; evaluation of serotonin-1A agonists; other 5-HT receptors; and additional studies and activities.
A motorized motion testing device modeled after a Ferris wheel was constructed to perform motion sickness tests on cats. Details of the testing are presented, and some of the topics covered include the following: xylazine-induced emesis; analysis of the constituents of the cerebrospinal fluid (CSF) during motion sickness; evaluation of serotonin-1A (5-HT sub 1A) agonists; other 5HT receptors; antimuscarinic mechanisms; and antihistaminergic mechanisms. The ability of the following drugs to reduce motion sickness in the cats was examined: amphetamines, adenosinergic drugs, opioid antagonists, peptides, cannabinoids, cognitive enhancers (nootropics), dextromethorphan/sigma ligands, scopolamine, and diphenhydramine.
Thirty femal cats were subjected to a motion sickness stimulus in three series of tests. A series consisted of five tests given biweekly, weekly, or daily. Each test consisted of 30 min of stimulation followed by 1 min of rest, and series were separated by a period of not less than 14 d. Retching was the dependent variable. No habituation (reduction in the incidence of retching) was found with biweekly testing but pronounced habituation was observed with weekly and daily testing. The 30 cats were divided evenly into high and low susceptibility groups based on the results of the biweekly tests. The rate of habituation was the same for the two susceptibility groups in both the weekly and daily series.
Experiments were performed to determine if suppression of motion-induced emesis (motion sickness) by 8-OH-DPAT altered the development or retention of habituation to the motion stimulus. Cats received 8-OH-DPAT followed by provocative motion on three consecutive treatment days. A drug-free test on the fourth day resulted in an incidence of emesis that was not different from that obtained on the fourth consecutive day of drug-free motion testing. Three consecutive days of treatment with 8-OH-DPAT without motion had no effect on the incidence of motion sickness on the fourth day. It was concluded that suppression of motion sickness by 8-OH-DPAT does not alter the acquisition or retention of habituation.
A method for the alleviation of both motion sickness and chemically-induced emesis is provided which includes the administration of a nontoxic, therapeutically effective amount of a composition which stimulates serotonin-1A receptors in a mammal in need of such treatment. The preferred compounds for use are buspirone and 8-hydroxy-2(di-n-propylamino)-tetralin (8-OH-DPAT).
The cerebrospinal fluid drawn from the fourth ventricles of the brains of cats during and after the development of motion sickness was studied to determine what neurotransmitters may be involved in the development of the sickness. The analytical procedure, which uses HPLC coupled with n-electrode coulometric electrochemical detection to measure many compounds with picogram sensitivity, is described. Baseline levels of DOPAC, MHPGSO4, uric acid, DA, 5-HIAA, and HVA were lower on motion and control days in cats which became motion sick when compared with cats which did not. None of the total of 36 identified compounds identified in the samples varied as a function of either exposure to motion or provocation of emesis. It is concluded that susceptibility to motion sickness is a manifestation of individual differences related to fundamental neurochemical composition.
Vomiting was suppressed in cats pretreated with 8-OH-DPAT and then challenged with an emetic stimulus; motion, xylazine or cisplatin. The antiemetic effect is likely due to stimulation of postsynaptic serotonin-1A receptors. The most parsimonious explanation is that it acts at a convergent structure, presumably at or near the vomiting center. If so, 8-OH-DPAT may block emesis elicited by virtually any other stimulus. A supplementary experiment revealed that lorazepam suppressed motion sickness at a dose that produced ataxia, but did not suppress xylazine-induced emesis. These results do not support the possibility that the antiemetic effects of 8-OH-DPAT were the result of anxiolytic activity.
The suitability of the two-parameter Weibull distribution for describing highly censored cat motion sickness latency data was evaluated by estimating the parameters with the maximum likelihood method and testing for goodness of fit with the Kolmogorov-Smirnov statistic. A procedure for determining confidence levels and testing for significance of the difference between Weibull parameters is described. Computer programs for these procedures may be obtained from an archival source.
The ability of buspirone to prevent motion sickness and the mechanism of the buspirone action were tested in cats pretreated (s.c. injection) by buspirone 30 min before being subjected to motion stimulus (in a device described by Crampton and Lucot, 1985) or to an injection of an emetic drug xylazine (using only cats susceptible to motion sickness or to xylazine, respectively). Buspirone treatment was found to block motion sickness with an effective dose-50 of 0.46 mg/kg. Buspirone pretreatment (with 4.0 mg/kg) has also significantly blocked vomiting in cats later injected with 0.66 mg/kg xylazine. The results indicate that buspirone is acting at the vomiting center, the point of convergence for the separate mechanisms subserving chemically-induced emesis and motion sickness.
The possible role of the alpha-2 adrenoceptors in xylazine-induced vomiting and in motion sickness was investigated. Cats were divided into two groups according to motion sickness susceptibility and were observed after s.c. injections of xylazine. The incidence of vomiting increased with the dose, and at each dose the high susceptibility group had a greater emetic incidence than the low susceptibility group. In another experiment with cats divided into two groups according to motion sickness susceptibility, s.c. administration of yohimbine effectively antagonized the xylazine-induced emesis in both susceptibility groups. The cats in the latter experiment were then challenged with a motion sickness stimulus after s.c. pretreatment with yohimbine. Yohimbine failed to prevent motion sickness but did occasion an unexplained variability in the incidence of vomiting. These findings suggest that the emetic effect of xylazine results from stimulation of alpha-2 adrenoceptors but that these receptors are not fundamental to feline motion sickness. The fact that susceptibilities to xylazine-induced emesis and to motion sickness are correlated suggests a point of interaction other than the area postrema, which is known to be essential for xylazine-induced vomiting but not for motion sickness in the cat.