Procedural examination of behavioural sensitisation to morphine: lack of blockade by MK-801, occurrence of sensitised sniffing, and evidence for cross-sensitisation between morphine and MK-801.
Rats were tested in an open field, a "sniffing box" and an eight-arm maze, to examine in detail the behavioural changes induced by morphine (10mg/kg, i.p.) and MK-801 (0.1mg/kg, i.p.), either alone or in combination, during a 10 day treatment and subsequent drug challenges. In addition to locomotion, a number of other behaviours such as sniffing, rearing and exploration were examined. After morphine challenge, sensitised locomotion and rearing were found in the open field, and sensitised sniffing and turning were observed in the sniffing box. In addition, in the sniffing box, saline challenge produced significant conditioned sniffing and turning, and after a challenge with MK-801, sensitised sniffing and turning were seen in the group pretreated with morphine, suggesting a cross-sensitisation between morphine and MK-801 (but not vice versa). In the eight-arm maze, sensitised locomotion was found after morphine challenge. Morphine and MK-801 changed the preference for particular angles run during trials in a characteristic manner. In none of the behavioural measures was MK-801 able to block the development (and expression) of sensitisation to morphine. In several cases, rather, MK-801 enhanced the acute morphine effects. Sensitisation of sniffing suggests that sensitisation has also developed within the nigrostriatal dopamine system and not only within the mesolimbic dopamine system, as is generally discussed in the context of the most commonly assessed behaviour, locomotion. This finding argues for the additional use of the sniffing box in sensitisation experiments.
Department of Neuropharmacology, Zoological Institute, University of Tübingen, Mohlstr. 54/1, 72074 Tübingen, Germany.
T.M.
TM
Tzschentke
W.J.
WJ
Schmidt