Zeitschrift für klinische Toxikologie
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Positive Effect of Nitric Oxide on Morphine-Induced Place Conditioning in Wistar Rats Treated by Colchicine Intra-Hippocampal CA1

Soheila Porkhodadad, Manizheh Karami and Mohammad Reza Jalali Nadoushan

Colchicine is a potent alkaloid neurotoxin known as a selective neurotoxin of granular cells of hippocampal formation. This research aimed to assess the consequences of hippocampal reward circuitry damaged by colchicine. Male Wistar rats were examined for saline conditioning a week after receiving of colchicine (1-8μg/rat, intra-CA1). Control group was simply microinjected saline (1μl/rat, intra-CA1). In addition, two categories of animals pre-treated by colchicine (2,8μg/rat, intra-CA1) were evaluated for place preference induced of morphine (2.5-7.5 mg/kg, s.c.) using a three-day schedule of unbiased paradigm. Also sham operated legend “normal” group passed the conditioning by morphine. This group was pre-treated saline (1μl/rat, intra-CA1) instead of colchicine. According to the results, the injection of colchicine (1-8μg/rat, intra-CA1) induced a place aversion in saline conditioning at the higher doses (8μg/rat). Furthermore, the colchicine treated rats showed histologically a significant ( p<0.001 ) decrease in numbers of pyramidal cells of CA1. On the other hand, morphine induced a significant place preference in animals pre-treated by colchicine (2,8μg/rat, intra-CA1). Moreover, pre-microinjection of L-arginine (0.3- 3μg/rat, intra-CA1), a precursor of nitric oxide (NO), pre-testing of morphine response caused a positive effect on expression of response to morphine. However, this effect was reversed when L-NAME (0.3-3μg/rat, intra-CA1) was injected into the CA1 prior to the administration of L-arginine (3μg/rat, intra-CA1). Based on data the neurotoxin, colchicine, may affect the place conditioning reward circuitry via decreasing of pyramidal cells in the CA1 area ( p<0.01 ), an effect which most likely can be improved by morphine administration peripherally. In conclusion the molecule NO into CA1 may have a positive force on morphine-induced place conditioning in Wistar rats received colchicine intra-CA1.