The clarification of responsible brain region and molecule underlying the expression of drug seeking behavior ("craving")

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We clarified following points involved in the relapse to methamphetamine (MAP) seeking behavior.1. MAP-seeking behavior induced by the MAP-associated cues and MAP-priming injection was attenuated by the intracranial administration of a cannabinoid CB_1 receptor (CB1R) antagonist, AM251 into the nucleus accumbens core (NAC) and prelimbic cortex (PrC). In these regions, the attenuating effects of AM251 on the relapse induced by each stimulus were blocked by the intracranial administration of mecamylamine, a non-selective nAChR antagonist, but not by scopolamine, a non-selective muscarinic ACh receptor (mAChR) antagonist. These findings suggest that relapses to MAP-seeking behavior may be due to the inactivation of nAChR following inhibition of ACh transmission via the activation of CB1Rs.2. The electric foot shock stress in the environment where MAP was self-administered induced MAP-seeking behavior. Meanwhile, CRF receptor antagonist suppressed MAP-seeking behavior. This result suggests … More that MAP-seeking behavior may be due to the activation of CRF receptors.3. The radical scavenger, edaravone suppressed MAP-seeking behavior. This result suggests that MAP-seeking behavior may be due to the activation of the production of radical.4. Intracranial administration of AM251 into the basolateral amygdala (BLA) attenuated the reinstatement of MAP-seeking behavior induced by MAP-associated cue. However, Intracranial administration of AM251 into the BLA did not attenuate MAP-seeking behavior induced by MAP-priming. These findings suggest that the MAP-associated cue and MAP-priming have a different mechanism underlying the expression of MAP-seeking behavior.5. The attenuation of MAP-seeking behavior by AM251 into the BLA was significantly reversed by co-microinjection of AMPA receptor antagonist DNQX into the NAC or PrC. These findings suggest that the MAP-seeking behavior induced by MAP-associated cue may be due to the inactivation of glutamatergic neurotransmission of the BLA to the NAC and PFC via the activation of CB1Rs. Less