STRIATAL EXTRACELLULAR DOPAMINE IN CONSCIOUS VS ANESTHETIZED RATS - EFFECTS OF CHLORAL HYDRATE ANESTHETIC ON RESPONSES TO DRUGS OF DIFFERENT CLASSES

Many investigations using the microdialysis technique have been performed in anesthetized animals, both in this laboratory and elsewhere. Concern arises with this preparation that the anesthetic may compromise neuronal function, or that it may interact with test drugs affecting neurotransmitter overflow. In addition, in these studies the microdialysis probe typically is introduced into the brain on the day of testing, and data collection commences within an hour or two following probe insertion. It has been suggested that transmitter recovered in the perfusate probably represents leakage due to tissue damage as well as exocytotic release, and may not accurately reflect neuronal responses to the manipulations of interest. Such potential confounds present important implications for the interpretation of data from these studies. The present investigation examined the effects of chloral hydrate anesthetic on (1) basal dopamine (DA) overflow in the anterior striatum, and (2) DA responses to systemically delivered drugs of two different classes known to influence DA activity. Three putative indices of impulse-dependent release were measured: (a) the time course and stability of basal DA overflow over several hours; (b) sodium channel involvement by adding tetrodotoxin (TTX) to the artificial CSF; and (c) calcium channel involvement using magnesium (Mg) in a calcium-free perfusate. Basal DA levels became stable in both conscious and anesthetized preparations by the second hour after probe insertion. Levels of recovered DA overflow in the anterior striata of conscious rats were approximately double those in chloral hydrate-anesthetized rats. Consistent with other findings, this suggests a general depression of CNS function by chloral hydrate. Basal DA was both TTX- and Mg-sensitive, indicating that most of the DA sampled probably arose from exocytotic release. DA response to D-amphetamine differed in the two preparations when expressed as a function of baseline. This reflected both the differences in absolute baseline levels and the impulse-independent mechanism of action of the drug. In contrast, systemic morphine resulted in an increase of DA overflow in anesthetized rats only, an elevation of DOPAC levels in both preparations, and an increase in HVA only in conscious animals. Morphine-treated rats received lower levels of anesthetic supplements over time than did controls, however. Presumably, this resulted in a diminished chloral hydrate suppression both of DA and of metabolite clearance.