Comparison of the effects of intracranial injections of 6-OHDA and guanethidine on consummatory behavior and monoamine depletion.

6-Hydroxydopamine (6-OHDA) has been used extensively to study the effects of catecholamine depletion on feeding and drinking behavior. The results from these experiments are variable and do not clarify the involvement of catecholamines in these behaviors. Guanethidine, which has been used in studies of the peripheral autonomic nervous system, provides an alternative method of catecholamine depletion. In the experiments reviewed here the effects of injections of 6-OHDA and guanethidine into the rat brain on consummatory behavior and temperature regulation have been compared and related to changes in monoamine levels as shown by fluorescence histochemistry. Injections of 6-OHDA into anterior hypothalamic areas have lethal effects on food deprived animals. This effect may be explained in terms of loss of ability to regulate temperature. Animals whose catecholamines were depleted by guanethidine injections into anterior lateral hypothalamus showed a consistent reduction in food and water intake and an elevation of body temperature. Reconciliation of these findings appears difficult. However, a comparative study of the intracranial diffusion patterns of guanethidine and 6-OHDA has revealed marked differences in the extent of diffusion as seen with the fluorescence histochemical method when injected acutely or chronically into the lateral hypothalamus, the substantia nigra or the amygdala of the rat brain. Cannulation damage extended up to 1 mm in diameter. Generalized damage was far greater for 6-OHDA (2 mm) than for guanethidine (0.3 mm). At the doses used guanethidine, but not 6-OHDA caused specific damage to catecholamine-containing neurons up to a distance of at least 3 mm from the cannula tip. Guanethidine was less selective for dopaminergic compared to noradrenergic neurons. These differences between the effects of the two drugs are explained in terms of their unique pharmacological properties and their estimated decay in CNS tissue. An attempt has been made to account for the differences in behavioral data and in particular the variability of the 6-OHDA data in terms of the differences in the type of damage produced by the two drugs and the extent of their diffusion. It is also argued that the different patterns of damage would not easily be distinguished by biochemical analysis, and further, that changes in injection volume and concentration may lead to different damage patterns.