Robert A. Dielenberg

The cardiovascular and behavioral response to cat odor in rats: unconditioned and conditioned effects.

Cardiovascular and behavioral responses were recorded in rats during exposure to cat odor. Rats were habituated to an open rectangular arena that contained a small enclosed wooden box in which they could hide. On day 1 of the experiment, after 30 min in the apparatus, rats were presented with a piece of fabric collar for 60 min. On day 2, rats were presented with an identical piece of fabric collar, except that it had been worn by a cat and therefore exuded cat odor. On day 3, rats were again presented with an unworn cat collar, to determine any conditioned responses to the environment or stimulus (collar) previously associated with cat odor. Results showed significantly increased blood pressure and decreased activity during exposure to cat odor as well as avoidance of the odor stimulus and an increase in vigilance and risk-assessment measures. No significant change in heart rate was found during cat odor exposure. On day 3, a transient increase in blood pressure was seen as well as reduced activity and a range of defensive behaviors. This suggests some conditioning of fear to a context in which cat odor had previously been experienced. Heart rate was also significantly decreased on day 3. A transient rise in blood pressure was also seen when the unworn cat collar was placed into the apparatus on day 3, suggesting a conditioned response to a stimulus that has been previously associated with cat odor. This study demonstrates that a natural stressful stimulus can induce both unconditioned and conditioned autonomic and behavioral responses.

Differential anxiolytic efficacy of a benzodiazepine on first versus second exposure to a predatory odor in rats

Abstract Rationale and objectives: Rodents tested in the elevated plus maze model of anxiety only show an anxiolytic response to benzodiazepines on their first exposure to the maze. The present study investigated whether a similar phenomenon occurs with benzodiazepines in a different model of anxiety that involves exposing rats to the odor of a predator. Methods: Testing took place in a rectangular arena containing a cat odor-exuding collar at one end and a small ”hide box” at the opposite end. Rats were initially familiarized with the odor-free apparatus for 20 min and then placed back in the apparatus 24 and 48 h later in the presence of cat odor. Results: Vehicle-treated rats displayed marked avoidance of the cat odor on both first and second exposures, spending most of the session in the hide box and very little time near the odor source. In contrast, rats given a low dose of midazolam (0.375 mg/kg) during first exposure spent considerable time in close proximity to the odor source and much less time in the hide box. Rats given midazolam (0.375 mg/kg) on their second exposure to cat odor displayed no such anxiolytic effect of the drug. Rats given midazolam (0.375 mg/kg) on both exposures showed a potent anxiolytic effect of the drug on each occasion. This pattern of results was replicated with a higher dose of midazolam (0.75 mg/kg). A further experiment showed that rats previously exposed to cat odor showed high levels of hiding in the test environment 24 h later even when the cat odor was no longer present. This conditioned fear was blocked by midazolam (0.75 mg/kg) suggesting that the ineffectiveness of midazolam on second exposure to cat odor is not due to a failure of the drug to affect conditioned fear. Conclusions: The ineffectiveness of midazolam in odor-experienced rats parallels the results obtained with benzodiazepines in the elevated plus maze. Such results may help illuminate the comparative lack of efficacy of benzodiazepines in treating certain types of anxiety disorders in humans.

Effect of dorsal periaqueductal gray lesions on cardiovascular and behavioral responses to cat odor exposure in rats

Previously we demonstrated Fos expression in the dorsal periaqueductal gray (DPAG) of the rat following cat odor exposure. Further work correlated the response to cat odor with a sustained blood pressure increase and deployment of defense behavior. It was therefore of interest to determine whether lesions of the DPAG would abolish these two effects of cat odor exposure. Male Wistar rats were given excitotoxic NMDA (N-methyl-D-aspartate) lesions of the DPAG and anterior tectum under halothane, then implanted with blood pressure telemetric probes. Sham lesions were made with saline. Rats were then exposed to cat odor with a hide option, followed 2 weeks later by re-exposure to cat odor without a hide option. Controls were exposed to rat odor in the same way. Trends toward attenuation in defense and cardiovascular indices were found in lesioned rats for cat odor exposure with a hide option, but these were not significant. Re-exposure to cat fur without a hide option enhanced the cardiovascular response and under these conditions, lesioned rats showed a significant change of the heart rate and locomotor activity response to cat fur. However, the blood pressure response was not significantly attenuated. Thus, the present results support the Fos data and indicate that the DPAG is involved in the expression of some but not all of the cardiovascular and behavioral components of the response to cat odor.

Effect of dorsal periaqueductal gray lesion on cardiovascular and behavioural responses to contextual conditioned fear in rats

Contextual conditioned fear in the rat is characterized by a freezing immobility associated with a marked increase in blood pressure, a slow increase in heart rate, and ultrasonic vocalizations. A previous Fos study also revealed a marked activation of the ventrolateral part of the periaqueductal gray (VLPAG) and a much smaller activation of its dorsal part (DPAG). Recent chemical blockade experiments indicate that the main role of the VLPAG in the response is to impose the immobility necessary for the expression of the freezing component. We now test the role of the DPAG to see if its small activation (as revealed by Fos) is of any functional significance in the contextual fear response. Large N-methyl-D-aspartate (NMDA) excitotoxic lesions that destroyed most of the DPAG were made in 10 rats. Another group of 10 rats had sham lesions with saline. The animals were then implanted with blood pressure telemetric probes, fear conditioned, and finally tested. There was no significant difference in the amount of freezing and in the blood pressure response between the two groups. However, there was a complete abolition of ultrasonic vocalizations and a significantly greater increase in heart rate in the DPAG-lesioned group. The effect on vocalization and heart rate may be explained by lesion of adjacent structures: the lateral PAG and the superior colliculus (baroreflex alteration), respectively. Thus, most of DPAG appears to play little role in the expression of the contextual fear response.

Cannabinoids increase conditioned ultrasonic vocalisations and cat odour avoidance in rats: Strain differences in drug-induced anxiety

AIMS Genetic disposition modulates the psychoactive effects of cannabis. Cannabinoids have a greater impact on brain regions that subserve anxiety in Wistar compared to Lewis strain rats. Here we aim to show that this correlates with strain differences in cannabinoid-induced anxiety-related behaviour. MAIN METHODS Lewis and Wistar rats were administered vehicle or the synthetic cannabinoid receptor agonist, CP 55,940 (10, 25 and 50μg/kg) before testing in the conditioned ultrasonic vocalization (USV), cat odour avoidance or open area avoidance models. KEY FINDINGS Animals were placed in a chamber in which they had previously received footshock. Wistar but not Lewis rats re-exposed under the influence of all CP 55,940 doses emitted significantly more USVs than vehicle-treated rats. In the cat odour avoidance model, rats were exposed to cat odour and given the opportunity to hide in a small box. In Wistar but not Lewis rats, 50μg/kg of CP 55,940 magnified hiding behaviour promoted by cat odour exposure. Animals were also tested in the open area avoidance model which occurred in the same arena as the predatory avoidance model but without cat odour. In Wistar, but not Lewis rats, 25 and 50μg/kg of CP 55,940 increased the avoidance of the open space. SIGNIFICANCE CP 55,940 increased anxiety-related behaviour in Wistar rats but not Lewis rats providing a model to dissect the genetic basis of cannabinoid-induced anxiety. We show for the first time that cannabinoids magnify conditioned USVs and cat odour avoidance behaviour dependent on the strain being tested.