Catecholamine involvement in lateral hypothalamic self-stimulation : with special reference to the dorsal noradrenergetic system

Corbett, Ronald Dale (1974) Catecholamine involvement in lateral hypothalamic self-stimulation : with special reference to the dorsal noradrenergetic system. Masters thesis, Memorial University of Newfoundland.

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Abstract

Six experiments were undertaken to determine the involvement of the nigrostriatal dopamine (DA) pathway and the dorsal noradrenergic (NA) pathway in mediating lateral hypothalamic (LH) self-stimulation. All subjects were implanted with bipolar electrodes in the LH area and were trained to self-stimulate. Once this behavior had stabilized (20-30 days), lesions at various levels of the nigrostriatal DA system and the dorsal NA system were made via intracerebral injections of the catecholamine (CA) neurotoxin, 6-hydroxydopamine (6-OHDA) and/or electrolytic lesions. Testing for self-stimulation was resumed 24 hrs. after the lesions and continued for a period of 5 days. At the conclusion of testing, the animals were sacrificed and prepared for histological examination. -- Destruction of several CA systems by injections of 6-OHDA (8μg/4μl) in the cells of origin (A9) of the nigrostriatal DA system resulted in a strong suppression of LH self-stimulation (p<.025). Injections of 6-OHDA (8μg/4μl) anterior to the cells of origin (A6) of the dorsal NA system had little or no effect on LH self-stimulation (Experiment 2). 6-OHDA (4μg/μl) and electrolytic lesions of the dorsal NA bundle in combination with electrolytic lesions of A6 also failed to substantially affect LH self-stimulation (Experiments 3 & 5). The fourth experiment attempted to further examine the role of the dorsal NA system in LH self-stimulation by injections of procaine ( a local anesthetic), d-amphetamine and glutamate (a neural excitant) directly in A6. All three treatments resulted in considerable suppression of LH self-stimulation (p<.001) but these results were rendered questionable due to possible non-specific effects and methodological considerations. The sixth and final experiment revealed that self-stimulation is rapidly obtained from the region of A6 when a sensitive shaping procedure that maximizes behavioral arousal is employed. -- Together; these results suggest that LH self-stimulation is mediated by the nigrostriatal and mesolimbic DA systems alone or in combination with the dorsal NA system but the dorsal NA system itself does not seem necessary for maintenance of LH self-estimulation. Thus, noradrenergic theories of self-stimulation (e.g. Stein & Wise, 1971) must be reconsidered.

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