Ms. Gevaerd et al., Combined effects of diethylpropion and alcohol on locomotor activity of mice: participation of the dopaminergic and opioid systems, BRAZ J MED, 32(12), 1999, pp. 1545-1550
Citations number
32
Categorie Soggetti
Medical Research General Topics
Journal title
BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH
The widespread consumption of anorectics and combined anorectic + alcohol m
isuse are problems in Brazil. In order to better understand the interactive
effects of ethanol (EtOH) and diethylpropion (DEP) we examined the locomot
ion-activating effects of these drugs given alone or in combination in mice
. We also determined whether this response was affected by dopamine (DA) or
opioid receptor antagonists. A total of 160 male Swiss mice weighing appro
ximately 30 g were divided into groups of 8 animals per group. The animals
were treated daily for 7 consecutive days with combined EtOH + DEP(1.2 g/kg
and 5.0 mg/kg, ip), EtOH(1.2 g/kg, ip), DEP (5.0 mg/kg, ip) or the control
solution coadministered with the DA antagonist haloperidol (HAL, 0.075 mg/
kg, ip), the opioid antagonist naloxone (NAL, 1.0 mg/kg, ip), or vehicle. O
n days 1, 7 and 10 after the injections, mice were assessed in activity cag
es at different times (15, 30, 45 and 60 min) for 5 min. The acute combinat
ion of EtOH plus DEP induced a significantly higher increase in locomotor a
ctivity (day 1: 369.5 +/- 34.41) when compared to either drug alone (day 1:
EtOH = 232.5 +/- 23.79 and DEP = 276.0 +/- 12.85) and to control solution
(day 1: 153.12 +/- 7.64). However, the repeated administration of EtOH (day
7: 314.63 +/- 26.79 and day 10: 257.62 +/- 29.91) or DEP (day 7: 309.5 +/-
31.65 and day 10: 321.12 +/- 39.24) alone or in combination (day 7: 459.75
+/- 41.28 and day 10: 427.87 +/- 33.0) failed to induce a progressive incr
ease in the locomotor response. These data demonstrate greater locomotion-a
ctivating effects of the EtOH + DEP combination, probably involving DA and/
or opioid receptor stimulation, since the daily pretreatment with HAL (day
1. EtOH + DEP = 395.62 +/- 11.92 and EtOH + DEP + HAL = 371.5 +/- 6.76; day
7: EtOH + DEP = 502.5 +/- 42.27 and EtOH + DEP + HAL = 281.12 +/- 16.08; d
ay 10: EtOH + DEP = 445.75 +/- 16.64 and EtOH + DEP + HAL = 376.75 +/- 16.4
) and NAL (day I: EtOH + DEP = 553.62 +/- 38.15 and EtOH + DEP + NAL = 445.
12 +/- 55.67; day 7. EtOH + DEP = 617.5 +/- 38.89 and EtOH + DEP + NAL = 41
8.25 + 61.18; day 10: EtOH + DEP = 541.37 +/- 32.86 and EtOH + DEP + NAL =
427.12 +/- 51.6) reduced the locomotor response induced by combined adminis
tration of EtOH + DEP. These findings also suggest that a major determinant
of combined anorectic-alcohol misuse may be the increased stimulating effe
cts produced by the combination.