α-Conotoxin TxIB Inhibits Development of Morphine-Induced Conditioned Place Preference in Mice via Blocking α6β2* Nicotinic Acetylcholine Receptors

Abstract

Morphine, the main component of opium, is a commonly used analgesic in clinical practice, but its abuse potential limits its clinical application. Nicotinic acetylcholine receptors (nAChRs) in the mesolimbic circuitry play an important role in the rewarding effects of abused drugs. Previous studies have showed that α6β2* (* designated other subunits) nAChRs are mainly distributed in dopaminergic neurons in the midbrain area, which regulates the release of dopamine. So α6β2* nAChRs are regarded as a new target to treat drug abuse. α-Conotoxin TxIB was discovered in our lab, which is the most selective ligand to inhibit α6β2* nAChRs only. Antagonists of α6β2* nAChRs decreased nicotine, cocaine, and ethanol rewarding effects previously. However, their role in morphine addiction has not been reported so far. Thus, it is worth evaluating the effect of α-conotoxin TxIB on the morphine-induced conditioned place preference (CPP) and its behavioral changes in mice. Our results showed that TxIB inhibited expression and acquisition of morphine-induced CPP and did not produce a rewarding effect by itself. Moreover, repeated injections of TxIB have no effect on learning, memory, locomotor activity, and anxiety-like behavior. Therefore, blocking α6/α3β2β3 nAChRs inhibits the development of morphine-induced CPP. α-Conotoxin TxIB may be a potentially useful compound to mitigate the acquisition and/or retention of drug-context associations.

αO-Conotoxin GeXIVA[1,2] Reduced Neuropathic Pain and Changed Gene Expression in Chronic Oxaliplatin-Induced Neuropathy Mice Model

“…The OFT apparatus was a square plastic box (40 × 40 × 35 cm); mice were placed at the center of the chamber and allowed to explore for 10 min. The behaviors of mice were recorded and analyzed by using the SMART 3 software (Panlab Harvard Apparatus, Barcelona, Spain) [48].…”

“…The EPM apparatus was an elevated maze (40 cm height) with two open arms and two closed arms (32 × 8.5 cm each). A mouse was placed in the central area and faced the open arm; 5 min of free exploration was recorded using a camera and analyzed using the SMART 3 software [48].…”

Mitogenome Characterization of Four Conus Species and Comparative Analysis

“…Most cone snails feed on polychaete worms, and others are either molluscivorous or piscivorous, with few species having more than one feeding pattern, which can generate an estimated 100,000 distinct conotoxins [2][3][4]. Additionally, owing to their exquisite potency and selective inhibitors of ion channel in the human brain, conotoxins have potential applications in medicine and physiology [5][6][7]. To comprehend how the great species diversity of the cone snails was generated and to interpret the origin of the different diet specializations, reconstructing a statistically robust phylogeny of cone snails is needed, which can enhance and improve the current discovery of pharmacologically important conotoxins [8,9].…”