Cannabinoid CB1 receptors of the rat central amygdala mediate anxiety-like behavior: interaction with the opioid system

Abstract

Cannabinoids, which are the active compounds of marijuana, produce some pharmacological effects similar to the opioids. In addition, there are functional interactions between the cannabinoid and opioid systems. In this study, we investigated the effects of intraperitoneal (i.p.) injection of opioid drugs on responses induced by intracentral amygdala (intra-CeA) microinjection of cannabinoid CB1 receptor agents in rats, using the elevated plus maze test of anxiety. I.p. injection of morphine (6 and 9 mg/kg) 30 min before testing, increased the percentage open arm time (%OAT) and the percentage open arm entries (%OAE), but not locomotor activity, showing an anxiolytic-like response. I.p. administration of the opioid receptor antagonist, naloxone (1 mg/kg) 15 min before testing, significantly reduced %OAT, but not %OAE and locomotor activity. The drug, however, tended to decrease locomotor activity. Intra-CeA administration of arachidonylcyclopropylamide (ACPA, an agonist shown to selectively activate CB1 receptors; 1.25 and 5 ng/rat) increased %OAT and %OAE but not locomotor activity, indicating an anxiolytic-like response. Coadministration of morphine (6 mg/kg, i.p.) plus ACPA (0.125 ng/rat, intra-CeA) increased the anxiolytic-like response. Administration of naloxone reversed the effects of intra-CeA injection of ACPA. Intra-CeA administration of the cannabinoid CB1 receptor antagonist, AM251 (2.5, 25, and 100 ng/rat) did not alter %OAT and %OAE, but the higher doses of the drug (25 and 100 ng/rat) reduced locomotor activity. Coadministration of morphine (6 mg/kg) or naloxone (0.1 mg/kg) with AM251 showed an anxiolytic-like response. In conclusion, the results may indicate an anxiolytic-like effect for cannabinoid CB1 receptors of the CeA and the existence of an interaction between the cannabinoid and the opioid systems in the modulation of anxiety.

Obestatin prevents analgesic tolerance to morphine and reverses the effects of mild morphine withdrawal in mice

“…To our knowledge this is the first study which has confirmed this effect of naloxone-precipitated mild morphine withdrawal in the open field test in mice. In contrast to the data obtained in mice, morphine administration increased %OAT and %OAE in rats [32][33][34] and decreased these parameters during morphine withdrawal [21,35]. In line with literature, naloxone alone did not alter the behavior of mice in our experiments [22,36].…”

Double Dissociation of Monoacylglycerol Lipase Inhibition and CB1 Antagonism in the Central Amygdala, Basolateral Amygdala, and the Interoceptive Insular Cortex on the Affective Properties of Acute Naloxone-Precipitated Morphine Withdrawal in Rats

“…As well, both the BLA and the CeA receive input from the interoceptive insular cortex (IC;McDonald, 1998;McDonald et al, 1999), which also has been implicated in both addiction and nausea processes (Contreras et al, 2007). As CB 1 agonism in the BLA (Ganon-Elazar and Akirav, 2009), but CB 1 antagonism in the CeA (Zarrindast et al, 2008), produces stress-relieving and anxiolytic effects in rats in aversive environments, we predicted that MJN110 in the BLA, but AM251 into the CeA, would reduce the aversive properties of MWD. Inactivation of the interoceptive IC has recently been demonstrated to prevent the acquisition of a naloxone-precipitated MWD CPA in rats (Li et al, 2013).…”

Cannabinoid Receptors Provide New Targets in Battling Anxiety

“…Studies using direct agonists of the ECS including Delta -9-THC, WIN55-212,2, Anandamide, and others have shown that CB1 is responsible for the primary psychoactive effects associated with cannabis ingestion. The nature of the behavioral effects of these drugs on anxiety is biphasic, with low doses producing anxiolytic effects and anxiogenic effects emerging when high doses are administered [31]. In a mouse model of anxiety, the behavioral traits associated with anxiety can be ameliorated by injection of CB1 agonist into the dorsal hippocampus.…”