Biomedical subjects

Kusnandar Anggadiredja

Publications and source records attributed to Kusnandar Anggadiredja.

7 recordsLinked to original sources

PubMed2006

Suppression of methamphetamine-seeking behavior by nicotinic agonists.

To understand the mechanism of methamphetamine (MAP) craving from the viewpoint of nicotinic acetylcholinergic transmission, we examined the responsible site of the brain for anticraving effects produced by nicotinic agonists by using a MAP self-administration paradigm in rats. Systemic nicotine and an acetylcholinesterase inhibitor, donepezil, attenuated the reinstatement of MAP-seeking behavior by means of the activation of nicotinic acetylcholinergic receptors, but not muscarinic acetylcholinergic receptors, in the nucleus accumbens core, prelimbic cortex, amygdala, and hippocampus. Among these regions, with the exception of the hippocampus, we also found functional differences in this reinstatement. The nicotinic antagonist mecamylamine alone did not reinstate MAP-seeking behavior. These results suggest that the inactivation of nicotinic acetylcholinergic transmission may be an essential factor in the appearance of MAP-seeking behavior, and, thus, the normalization of the inactivated state may result in the suppression of the reinstatement. Our findings also indicate that there are functional differences in the responsible brain subregions. Extending this view to the treatment of MAP dependence, our results suggest that activators of nicotinic acetylcholinergic transmission are possible anticraving agents.

Acetylcholinesterase↗

PubMed2005

Decrease in prostaglandin level is a prerequisite for the expression of cannabinoid withdrawal: a quasi abstinence approach.

Cannabinoid withdrawal has been indicated in both human and animal subjects. One of pathways proposed to facilitate cannabinoid action is the arachidonic acid cascade. Previously, we have shown that prostaglandin attenuated the expression of withdrawal signs in tetrahydrocannabinol-dependent mice. It follows that the cascade might participate in the expression of cannabinoid withdrawal. We utilized a quasi abstinence approach (the induction of a state of cannabinoid withdrawal without giving any cannabinoid substances in a naïve animal) to describe the relationship between the change in prostaglandin level, an end product of the arachidonic acid cascade, and the expression of cannabinoid withdrawal. Administration of 10 mg/kg diclofenac, a prostaglandin synthesis inhibitor, i.p. 30 min before SR 141716A induced cannabinoid withdrawal signs in naïve mice, which were comparable to the true abstinence in cannabinoid-tolerant mice. In turn, 10 mg/kg Delta(8)-THC i.p., given 15 min prior to SR 141716A, blocked the expression of these signs. These results suggested that the decrease in prostaglandin level is a prerequisite for the expression of cannabinoid withdrawal.

Animals↗

PubMed2004

New perspectives in the studies on endocannabinoid and cannabis: a role for the endocannabinoid-arachidonic acid pathway in drug reward and long-lasting relapse to drug taking.

Growing evidence on the involvement of cannabinoids in the rewarding effects of various kinds of drugs of abuse has suggested that not only the classical dopaminergic and opioidergic, but also the most recently established endocannabinoid system is implicated in the brain reward system. Furthermore, the interplay between the three systems has been shown to be an essential neural substrate underlying many aspects of drug addiction including craving and relapse. Relapse, the resumption of drug taking following a period of drug abstinence, is considered the main hurdle in treating drug addiction. Yet, little is known about its underlying mechanisms. The link between the endocannabinoid system and the arachidonic cascade is currently being clarified. While several findings have, indeed, shown the essential role of the endocannabinoid system in the reinstatement model, the endocannabinoid-arachidonic acid pathway may also be an important part in the neural machinery underlying relapse. This evidence may provide an alternative approach that will open a novel strategy in combating drug addiction.

Amphetamine-Related Disorders↗

PubMed2004

Naltrexone attenuates cue- but not drug-induced methamphetamine seeking: a possible mechanism for the dissociation of primary and secondary reward.

The present study was aimed to clarify the role of the opioid system in the reinstatement of methamphetamine (METH)-seeking behavior in METH self-administering rats. Following 12 days of self-administration of METH, the replacement of METH with saline resulted in a gradual decrease in lever press responses (extinction). Under extinction conditions, METH-priming or re-exposure to cues previously paired with METH infusion markedly increased the responses (reinstatement of drug-seeking). Naltrexone administered 30 min before re-exposure to METH-associated cues attenuated reinstatement of drug-seeking behavior. On the other hand, administration of this antagonist had no effect on the reinstatement induced by METH-priming. We discussed these findings in relation with the dissociation of primary and secondary reward, suggesting that an opioid mechanism is responsible for this dissociation. Further, these results indicate the possibility of using naltrexone as an anti-relapse agent.

Animals↗

PubMed2004

Endocannabinoid system modulates relapse to methamphetamine seeking: possible mediation by the arachidonic acid cascade.

We clarified the modulating action of the endocannabinoid system, and its possible mediation by the arachidonic acid cascade, on the reinstatement of methamphetamine (METH)-seeking behavior, using the intravenous self-administration paradigm in rats. Following 12 days of self-administration of METH, the replacement of METH with saline resulted in a gradual decrease in lever press responses (extinction). Under extinction conditions, METH-priming or re-exposure to cues previously paired with METH infusion markedly increased the responses (reinstatement of drug-seeking). The cannabinoid CB1 receptor antagonist, SR141716A, blocked this behavior. Although the cannabinoid agonist, Delta8-tetrahydrocannabinol (THC), had no effects by itself, coadministration of the agonist and METH at small doses reinstated the drug-seeking behavior. THC attenuated the effects of the reinstatement-inducing dose of METH, but enhanced the effect of cues. Either given repeatedly during the extinction or singly, 24 h before the first METH-priming or cues challenge, THC suppressed the reinstatement. In another set of experiments, we found that diclofenac, a cyclooxygenase inhibitor, also attenuated the reinstatement induced by exposure to cues or drug-priming. These results suggest that the endocannabinoid system, through possible mediation by the arachidonic acid cascade, serves as a modulator of the reinstating effects of METH-priming and cues. Extending the current view on the treatment of drug dependence, these results indicate that endocannabinoid-activating substances as well as cyclooxygenase inhibitors may be promising as antirelapse agents.

Amphetamine-Related Disorders↗

PubMed2004

Nicotine attenuates relapse to methamphetamine-seeking behavior (craving) in rats.

This study clarifies the modulating action of the nicotinic cholinergic system on reinstatement of methamphetamine (MAP)-seeking behavior (craving) using an intravenous, self-administration paradigm in rats. After self-administration of MAP for 10 days, replacing MAP with saline solution (MAP withdrawal) gradually decreased lever-pressing responses. On the sixth day of MAP withdrawal, MAP (1.0 mg/kg, i.p.)-priming injection significantly increased lever-pressing responses (reinstatement of MAP-seeking behavior). This MAP-seeking behavior was attenuated by repeated nicotine administration for 5 days during MAP withdrawal, and this attenuating effect was antagonized by the nicotinic antagonist mecamylamine. These results suggest that the appearance of MAP-seeking behavior may be due to inactivation of the nicotinic cholinergic neuron. Furthermore, it is suggested that nicotinic activating agents may be useful in preventing relapse to drug abuse.

Amphetamine-Related Disorders↗

PubMed2003

Prostaglandin E2 attenuates SR141716A-precipitated withdrawal in tetrahydrocannabinol-dependent mice.

The present study aimed to clarify the role of the arachidonic acid cascade in mediating the expression of withdrawal signs in cannabinoid-dependent mice. Mice were injected with Delta(8)-tetrahydrocannabinol (THC) at 20 mg/kg (i.p.) every 12 h, 11 times. When SR141716A, a specific cannabinoid CB1 receptor antagonist, at 10 mg/kg (i.p.) was given 4 h after the last THC injection, withdrawal signs such as forepaw licking, facial preening, grooming, forepaw tremor, head shakes and weight loss were clearly observed. PGE(2) at 0.1, 1.0 and 3.2 microg (per animal; i.c.v.) given prior to SR141716A (10 mg/kg, i.p.) dose-dependently decreased the number of forepaw licking, facial preening, grooming and forepaw tremor episodes. Instead of SR141716A, a cyclooxygenase inhibitor diclofenac at 10 mg/kg (i.p.) also precipitated these withdrawal signs. The results suggest that the expression of THC withdrawal is due to a decrease in prostaglandin levels through inactivation of the arachidonic acid cascade in the brain.

Animals↗