Effects of lesioning noradrenergic neurones in the locus coeruleus on conditioned and unconditioned aversive behaviour in the rat.

1. The brain noradrenergic system may have a role in anxiety disorder. This study has examined the effect of bilateral 6-hydroxydopamine lesions of the noradrenergic neurones in the locus coeruleus (LC) of male Lister hooded rats on behaviour produced by unconditioned and conditioned aversive stimuli. 2. The 6-hydroxydopamine (4 microg) lesions markedly reduced the noradrenaline content of the locus coeruleus hypothalamus, frontal cortex and the periaqueductal grey area without altering the levels of either dopamine or 5-hydroxytryptamine measured 14 days after administration. 3. Exposure to ultrasound (20 kHz at 98 dB for 60 sec), an unconditioned aversive stimulus, induced a defence response in the rats characterised by an increase in activity (running and jumping) followed by a period of inactivity (freezing). 4. Lesioning of the LC significantly attenuated the duration of freezing but was without effect on the active phase of the response. A similar reduction in freezing behaviour was seen with LC lesions when rats were exposed (3 hours after the acquisition) to the contextual cue of the conditioned emotion response paradigm. 5. These findings confirm that the locus coeruleus is involved in the regulation of fear-related behaviour in the rat both in an unconditioned and a conditioned model. Furthermore the results indicate that noradrenaline modifies defence behaviour rather than being the principle activating mechanism.

Strain differences to the effects of aversive frequency ultrasound on behaviour and brain topography of c-fos expression in the rat.

Previous studies have shown that ultrasound at 20 kHz produces an escape (defence) response in the hooded Lister rat. This study compares the ultrasound-induced behavioural response in the hooded Lister and albino Wistar rat. Ultrasound (continuous tone, square wave, 20 kHz) produced an initial characteristic startle response (brisk running) in the hooded Lister rat that was followed immediately after cessation of the ultrasound by a period of freezing behaviour. In contrast, Wistar rats showed no initial escape response but a prolonged period of freezing that started during the ultrasound and continued for a period after the end of the ultrasound. Immunohistochemical assessment of c-fos expression also showed a difference between the two strains with preferential expression in the dorsal region of the rostral and caudal periaqueductal grey (PAG) in the hooded Lister rat, while the expression occurred in the ventral PAG in the Wistar rats. In summary, the two strains exhibit distinct defensive behaviours and patterns of neuronal activation in response to the same aversive signal. It remains to be determined whether these differences relate to neuronal circuitry or perception of the signal, but analysis of the mechanisms involved may help our understanding of the heterogeneity of anxiety disorders.