Persistent anxiogenic effects of a single or repeated doses of cocaine and methamphetamine: interactions with endogenous cannabinoid receptor ligands

Abstract

As persistent behavioural changes, such as increased anxiety-related behaviours, can be predicted based on the phenomenon of psychostimulant-induced neuronal plasticity, the time course (3-, 5- and 10-day time points) of the effects of both a single and repeated (daily for 7 days) i.p. administrations of cocaine (COC) and methamphetamine (MA) on anxiety-related behavioural symptoms in the elevated plus-maze test were examined in mice. Furthermore, based on the reported interactions between brain dopamine versus cannabinoid (CB) receptors and the contribution of CB receptors to the occurrence of persistent anxiety-related behavioural symptoms, the interactions of the agonist CP 55940 (CP) and the endogenous ligands anandamide (arachidonylethanolamide: AEA), 2-arachidonylglycerol (ARA), N-arachidonyldopamine (NADA), noladin ether (NL), and virodhamine (VA) with the COC- or MA-induced anxiety-related behaviours were also studied. In both an acute experiment using a single COC (30 mg/kg) or MA (4 mg/kg) dose and a chronic experiment using repeated COC (15 mg/kg) or MA (2 mg/kg) doses, anxiety-related behavioural symptoms were observed similarly at 3- and 5-day time points, but disappeared at the 10-day time point. Among the CB ligands, the agonists CP, AEA, ARA, NADA, and NL provided strong protective effects against each parameter at 3- and 5-day time points. Therefore, it was concluded that both COC and MA caused persistent anxiety-related behavioural symptoms following both a single and repeated treatments. Since these anxiogenic effects were attenuated by the endogenous CB agonists, the involvement of brain CB receptors was suspected.

Mice with Decreased Cerebral Dopamine Function following a Neurotoxic Dose of MDMA (3,4-Methylenedioxymethamphetamine, “Ecstasy”) Exhibit Increased Ethanol Consumption and Preference

“…Based on animal and human studies, it has been hypothesized that the anxiolytic property of ethanol or, in the case of humans, the belief that alcohol would relieve anxiety, could play a role in the drug-seeking behavior (Thomas et al, 2003) and that anxiety problems precede alcohol abuse (Cox et al, 1990). A recent study has shown that methamphetamine (which also induces long-term damage to dopamine neurons) caused persistent anxiety-related behavioral symptoms lasting for at least 5 days (Hayase et al, 2005). Nevertheless, the current study clearly shows that pretreatment with MDMA does not alter the behavior of the animals in the dark-light box 3 weeks after MDMA, which is the time at which ethanol consumption is greater than that observed in saline-treated mice.…”

Subchronic Cannabinoid Agonist (WIN 55,212-2) Treatment during Cocaine Abstinence Alters Subsequent Cocaine Seeking Behavior

“…Drug cues also can induce both cocaine craving and anxiety, paired with activation of the hypothalamic-pituitary-adrenal axis (Sinha et al, 2003), suggesting that overlap exists between neural substrates controlling craving evoked by drug cues and stress (Sinha et al, 2000;Weiss, 2005). Finally, the anxiogenic effects of cocaine can be attenuated by CB1 agonists (Hayase et al, 2005). Considering this evidence, one may speculate that the anxiolytic consequences of subchronic treatment with the highest dose of WIN 55,212-2 in the elevated plus maze test may have contributed to the attenuation of anxiogenic effects exerted by environmental cues during the extinction and cue reinstatement tests.…”

“…Interestingly, activation of CB1 receptors seems to attenuate the anxiogenic or stressful aspects of cocaine's actions. For example, anxiogenic effects associated with either single or repeated doses of cocaine in mice were attenuated by the CB1 agonists, CP 55,940, anandamide, 2-arachidonylglycerol, N-arachidonyldopamine, and noladin ether (Hayase et al, 2005). Moreover, recent cannabis use has been found to decrease stress-induced blood oxygen level-dependent (BOLD) signals in the frontal and cingulate cortices of cocaine dependent individuals (Li et al, 2005).…”

Interactions of Cannabis and Amphetamine-Type Stimulants

“…In addition, the calming and relaxing properties of cannabis may offset some of the psychological untoward consequences of ATS, such as anxiety and agitation. This possibility is supported by preclinical evidence in rodents subjected to both acute and chronic administration of METH [105]. However, cannabis has been shown to produce variable effects with respect to anxiety [106] and may even exacerbate some of the negative subjective sensations induced by ATSs, such as panic and paranoia.…”