Amnesia induced by halothane anaesthesia coexists with a reduction of the hypothalamus and amygdala galanin receptors affinity in the rat brain

Inmaculada Bellido1, Aurelio Gomez-Luque2
1D. Pharmacology and Clinical Therapeutic. Medicine School. University of Malaga, Malaga, Spain, 2S. Anesthesiology, Virgen de la Victoria Universitary Hospital, Malaga, Spain

General anaesthesia, at minimum, provides amnesia and unresponsiveness (Ozer at al., 2006). Although recovery is usually rapid, some patients report lingering difficulty with concentration and memory for days or weeks after surgery. Inhaled anaesthetics like halothane often produce depression of learning and amnesia in humans (Alkire et al., 2004). It has been reported that galanin impairs learning and memory (Wrenn et al., 2001; Wrenn et al., 2002; Elvander et al., 2005). The possible relationship between brain galaninergic receptors function and amnesia induced by anaesthesia with halothane (HAL) was studied.

All the experimental procedures followed the provisions and general recommendations of the European Communities Council Directive and were approved by local authorities. Male Sprague-Dawley rats (N= 24, 6 months old, weighted 256±12 g) were anaesthetized with 1 MAC HAL (1.8% inspired concentration) in oxygen for 1 h using a continuous flow vaporizator adapted to a hermetically close clear acrylic cylindrical chamber. The sham group underwent the same procedures with no use of HAL. The 8 arms radial labyrinth test was used to quantify the effect of halothane on the animals’ cognitive and memory function. The animals were trained to learn how to localize the food pellet by 14 trained sessions in the labyrinth test. Then the last training test was done 1 h before HAL anaesthesia and the final test was done 24 h post-anaesthesia. The Open-field test was used to quantify the effects of HAL in the motor and exploratory activity of the animals. The galanin receptors were characterized by competition experiment of 125I-Human galanin (0.4 nM) by porcine galanin 1-29 (0.001 nM to 1 <M) using autoradiography techniques in the hypothalamus and the amygdala (coronal sections were made at Bregma -3.6 mm).

Labyrinth test data show a reduction of the retrograde memory in HAL group: i) increased reaction time in the first accurate choice (+56.8%) and in the first 8 accurate choices (+72.98%); ii) reduced the ability to remember the location of food in the labyrinth arms (increased the number of completed (+96.1%) and partial (99.3%) error choices; and reduced the number of completed (-46.1%) and partial (-42.4%) correct choices, and the number of correct completed choices realized in the first 8 choices (-43.05%)(p<0.05). Thus HAL did not affect the locomotor activity in the open field test; the reduced response in the labyrinth test could not be related with a deficit of the locomotor function. HAL reduced the affinity of the galanin receptors in the hypothalamus (Sham Ki 0.701 ±0.33 nM and Halothane Ki 1.765 ±0.35 nM, increment of +151%) and amygdala (Sham Ki 0.390 ±0.03 nM and Halothane Ki 0.734 ±0.21 nM, increment of +88%) (p<0.01). No changes in the galanin receptors maximal bound (Bo) were detected.

Memory deficit observed after halothane anesthesia coexists with a reduction of the hypothalamus and amygdala galanin receptors affinity in the rat brain.

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