An analysis of the behavioural functions of the coeruleo-cortical noradrenergic projection
This thesis investigates the behavioural functions of the ascending noradrenergic projections from the locus coeruleus to forebrain regions such as the neocortex and hippocampus in the dorsal noradrenergic ascending bundle (DNAB). The behavioural effects of lesions to the DNAB were assessed during the neurotoxin 6-hydroxydopamine, which reduces cortical NA levels to about 5 percent of control values. The neuroanatomical specificity of the behavioural deficits was also assessed, either through comparison with the effects of lesions in the trajectory of the lateral tegmental NA cell bodies (ventral noradrenergic ascending bundle; VNAB), or dopamine (DA) depletion within the caudate nucleus or nucleus accumbens. In Chapter 3, the effects of DNAB lesions on learning were studied using 3 different behavioural paradigms: continuously food reinforced (CRF) lever pressing; conditioned emotional response (CER); and a place navigation task in a water maze. DNAB lesions had no effect on either the acquisition or extinction of CRF lever pressing, but impaired acquisition and produced a mild resistance to extinction of the CER. DNAB lesions had no effect on animals pretrained in the CER procedure, showing that the deficit is specific to learning. The neuroanatomical specificity of this acquisition impairment was demonstrated by comparison to VNAB lesions, which had no effect on the acquisition of the CER, but retarded its extinction. The possible contribution of stress to the induction of learning deficits in DNAB lesioned rats was assessed in a water maze. Two different water temperatures were used to manipulate stress; the DNAB lesion only impairing learning in the cold water. In contrast, the cold water reversed motoric, but not learning deficits caused by DA depletion within the caudate nucleus. In Chapter 4, the effects of DNAB lesions on responsivity to novel stimuli were also studied using a food neophobia test. DNAB lesions enhanced environmental neophobia, since they increased the latency to contact food in a novel, but not a pre-exposed open field. However, the tendency to choose the most palatable food, irrespective of novelty was also increased. VNAB lesions and systemic chlordiazepoxide were both shown to produce different behavioural effects to DNAB lesions. In Chapter 5, the effects of DNAB lesions on a 5 choice visual discrimination were assessed. The lesion was shown selectively to impair discriminative accuracy only if white noise was presented as a distractor, or stimulus presentations were temporally unpredictable. As amphetamine mimics the enhanced impulsivity of responding caused by these behavioural manipulations, the effects of systemic and intra-accumbens amphetamine in DNAB lesioned rats were studied. Again, discriminastive accuracy in DNAB lesioned rats was impaired, suggesting that DNAB lesions impair discriminative accuracy when DA mechanisms within the nucleus accumbens are activated. The effects of DA depletion within the nucleus accumbens were assessed in a control experiment, and was shown to selectively attenuate the speed and probability of responding, without affecting discriminative accuracy. The results are evaluated in the theoretical context of previous accounts of DNAB function, and it is concluded that the behavioural effects of DNAB lesions are likely to be heterogeneous, given the nature of its diverse projections.