Cerebroventricular tetrahydropapaveroline infusions and ethanol consumption in the rat

Discrepant results have been reported from different laboratories on the effects of tetrahydropapaveroline (THP) and related compounds. In order to try to explore the discrepancy, an independent researcher participated in a partial replication attempt at the laboratory from which reports had previously come that THP markedly increased ethanol consumption by rats and produced withdrawal-like behavior. Withdrawal-like signs were observed after several once-daily bilateral ventricular infusions of 1.0 microgram THP. These abnormal behaviors varied in frequency and intensity but continued up to the last day of infusion and were rated independently by up to 5 judges. The mean ethanol intake, however, during THP treatment remained virtually the same as before THP (mean g ethanol per kg body wt. +/- SE: 1.60 +/- 0.29 before THP, 1.69 +/- 0.45 during THP). Control rats drank similar amounts of ethanol (1.60 +/- 0.33 before vehicle infusions, 1.65 +/- 0.42 during vehicle infusions). The individual THP animals tended to show greater variations than the controls from their own pre-treatment levels, but none of them showed a mean increase of greater than 2.0 g/kg in ethanol intake. Injections of THP or noreleagnine into cannulae aimed at hippocampal and periventricular grey sites also failed to increase alcohol drinking; however because histology was not available, it is not known whether or not the sites of injection were located in these structures. In comparison to the previously published report of Myers and Oblinger (25), this experiment differed in several variables. It is concluded that the precise experimental parameters necessary for once-daily THP reliably to increase ethanol consumption remain to be determined.