Article Figures & Data
Figures
- Fig. 1.
Comparison of the specific binding of [3H]CP55,940 to cannabinoid receptors in saggital brain sections of wild-type and enkephalin-deficient mice. Specific binding is shown in the top panel. Unspecific binding, determined in the presence of 10 μm CP55,244, is shown in the bottom panel.
- Fig. 2.
Acute effects of THC are normal in enkephalin-deficient mice. Horizontal (a) and vertical (b) movements in the open field are similarly reduced in a dose-dependent manner in wild-type and knock-out mice. THC increases ring catalepsy (c) and reduces body temperature (d). Significant treatment effects, but no significant genotype effects, were detected using two-way ANOVA in all paradigms. Data are expressed as mean ± SE. *p ≤ 0.05; **p ≤ 0.01 determined by Scheffe's F test.
- Fig. 3.
Development of THC tolerance. a,Tolerance to temperature changes developed similarly in both genotypes.b, Body weights were determined each morning before the THC injection. Changes were calculated by subtracting the weight from the measurement on the previous day. Note that wild-type animals lost significantly more weight than enkephalin knock-out mice.c, No significant tolerance for the effects of THC on spontaneous activity was observed in knock-out or wild-type mice during the course of this experiment. d, THC analgesia was significantly reduced in enkephalin-deficient mice. e,Tolerance to the antinociceptive effects of THC developed slower in mutant mice. Significant differences between the two genotypes were found on days 1 and 2 of testing. Data are expressed as mean ± SE. *p ≤ 0.05 versus vehicle, **p ≤ 0.01 versus vehicle; ★p ≤ 0.05 +/+ versus −/−, ★★p ≤ 0.01 +/+ versus −/−.
- Fig. 4.
Severity of THC withdrawal syndrome is reduced in enkephalin-deficient mice. Abstinence was precipitated by the administration of the CB1 antagonist SR141716A (10 mg/kg, i.p.) after chronic THC or vehicle treatment. Seven of 10 abstinence signs were decreased in the knock-out mice. Counted (wet dog shakes, front paw tremor, and sniffing) and checked (tremor, ptosis, ataxia, mastication, hunched posture, piloerection, and penile lick) somatic signs of withdrawal were observed for 45 min immediately after SR 141716A administration. A global withdrawal score was calculated for each animal by giving each individual sign a relative weight. Values for the global score were from 0 to 100. Data are expressed as mean ± SE. *p ≤ 0.05 versus vehicle, **p ≤ 0.01 versus vehicle; ★p ≤ 0.05 +/+ versus −/−, ★★p ≤ 0.01 +/+ versus −/− (Scheffe'sF test).
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