Järbe Torbjörn U C, Lamb Richard J, Liu Qian, Makriyannis Alexandros
Department of Psychiatry, MCP Hahnemann University, Philadelphia, PA 19102, USA.
Eur J Pharmacol. 2003 Apr 11;466(1-2):121-7. doi: 10.1016/s0014-2999(03)01491-2.
The current study examined the interaction between the cannabinoid CB(1) receptor agonists Delta(9)-tetrahydrocannabinol and (R)-methanandamide in combination with the cannabinoid CB(1) receptor antagonist SR-141716A (N-(piperidin-1-yl)-5-(4-chloro-phenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide HCl) in rats responding for food on a fixed ratio (FR-10) schedule of food reinforcement. The study provided only limited evidence for antagonism by SR-141716A (at 1 mg/kg but not with 0.3, 3 and 10 mg/kg) of the rate suppressant effects induced by the cannabinoid CB(1) receptor agonist Delta(9)-tetrahydrocannabinol (and only at the single dose of 5.6 mg/kg Delta(9)-tetrahydrocannabinol). (R)-Methanandamide in combination with SR-141716A resulted in a greater rate suppression compared to that induced by (R)-methanandamide alone. Thus, SR-141716A augmented the rate-decreasing effects of (R)-methanandamide and only minimally altered the rate-decreasing effects of Delta(9)-tetrahydrocannabinol. Additionally, high doses (10 and 30 mg/kg) of SR-141716 singly consistently suppressed the rate of responding. The current results coupled with our previous data examining combinations of Delta(9)-tetrahydrocannabinol or (R)-methanandamide and SR-141716 (see text) underscore pharmacological/behavioral differences (whether quantitative or qualitative) between the cannabinoid CB(1) agonists (R)-methanandamide and Delta(9)-tetrahydrocannabinol revealed by their interactions with the cannabinoid CB(1) antagonist SR-141716.
本研究检测了大麻素CB(1)受体激动剂Δ9-四氢大麻酚和(R)-甲烷基大麻酰胺与大麻素CB(1)受体拮抗剂SR-141716A（N-(哌啶-1-基)-5-(4-氯苯基)-1-(2,4-二氯苯基)-4-甲基-1H-吡唑-3-甲酰胺盐酸盐）在大鼠按固定比率（FR-10）食物强化程序获取食物时的相互作用。该研究仅提供了有限的证据表明SR-141716A（1mg/kg时，而非0.3、3和10mg/kg时）对大麻素CB(1)受体激动剂Δ9-四氢大麻酚诱导的反应抑制作用有拮抗作用（且仅在5.6mg/kg这一单一剂量的Δ9-四氢大麻酚时）。与单独使用(R)-甲烷基大麻酰胺相比，(R)-甲烷基大麻酰胺与SR-141716A联合使用导致更大的反应抑制。因此，SR-141716A增强了(R)-甲烷基大麻酰胺的反应降低作用，而对Δ9-四氢大麻酚的反应降低作用影响极小。此外，高剂量（10和30mg/kg）的SR-141716单独使用时持续抑制反应率。当前结果与我们之前检测Δ9-四氢大麻酚或(R)-甲烷基大麻酰胺与SR-141716联合使用的数据（见正文）共同强调了大麻素CB(1)激动剂(R)-甲烷基大麻酰胺和Δ9-四氢大麻酚与大麻素CB(1)拮抗剂SR-141716相互作用所揭示的药理学/行为学差异（无论是定量的还是定性的）。
