Tetrahydropapaveroline induces small granular vesicles in brain dopamine fibres [24]

Tetrahydroisoqinolines (TIQs) can be formed by the condensation of catecholamines with aldehydes. Their in vivo formation has been postulated as a possible mechanism to explain some long-term effects of ethanol on the central nervous system^1,2. However, there have been several criticisms ^3,4 and reviews^5,6 of this hypothesis. Although TIQ formation may not explain all the effects of ethanol, TIQs can influence behaviour^7-9 and they do have transmitter-like properties: they can be formed in vivo^10-12; they can be taken up and released in vivo from the adrenergic plexus of the rat iris¹³; they can be taken up into rat brain synaptosome fractions¹⁴; and TIQs applied exogenously have been localised in peripheral catecholamine tissues with both fluorescence¹³ and electron microscopy¹⁵. Thus, TIQs may accumulate in specific brain regions and influence behaviour by either acting as false transmitters¹³ or by displacing endogenous transmitters. Critical to this TIQ hypothesis is the demonstration of TIQ uptake and localisation into central neurone terminals. In the present study, slices of rat caudate nucleus were incubated with TIQs and then examined with the electron microscope. The results provide evidence for both the uptake and localisation of the TIQ, tetrahydropapaveroline (THP), into central dopamine fibres and terminals. This localisation may prove important in understanding the mechanism by which TIQs influence animal behaviour and any possible role for TIQs in chronic alcohol consumption.