beta-funaltrexamine and salsolinol

Salsolinol (Sal), locally administered into the posterior VTA (pVTA) of rats, produces psychomotor responses and reinforcing effects, probably, through the activation of μ-opioid receptors (MORs). The neurochemical correlates of these phenomena are, however, practically unknown. In this paper, we explore the neurochemical events and the mechanisms involved in these behaviors. To do that, we test the ability of Sal, directly microinjected into the pVTA, to induce conditioned place preference (CPP) and to increase dopamine levels in the nucleus accumbens shell. Bilateral injections of 30 pmol of Sal induced a strong CPP (rats spent around 70% of the total test time), a result that could be explained by the fact that Sal microinjected into the pVTA increased DA levels in the ipsilateral accumbens up to 141% of baseline. The local pretreatment with β-FNA, an antagonist of MORs, prevented this increase, supporting our hypothesis on the involvement of MORs in the Sal-derived effects.

Topics: Animals; Conditioning, Operant; Dopamine; Isoquinolines; Limbic System; Male; Microdialysis; Microinjections; Naltrexone; Narcotic Antagonists; Nucleus Accumbens; Rats; Rats, Wistar; Receptors, Opioid, mu; Ventral Tegmental Area

Microinjections of ethanol and acetaldehyde into ventral tegmental area (VTA) produce locomotor activation in rats through mechanisms dependent on the mu-opioid receptors. However, it is not clear how these drugs can interact with these receptors. It has been hypothesized that salsolinol could be the responsible for this interaction.. The aim of the study was to investigate the ability of salsolinol to induce both motor activation and motor sensitization in rats after repeated intra-VTA administration.. Rats received one microinjection into the posterior VTA of artificial cerebrospinal fluid (aCSF; 200 nL), salsolinol (0.3-3,000.0 pmol/200 nL), or salsolinol (30.0 pmol/200 nL) with either naltrexone (13.2 nmol/200 nL) or with the antagonist of the mu-opioid receptors, beta-funaltrexamine (beta-FNA; 2.5 nmol/300 nL). In the sensitization experiments, four microinjections of salsolinol (30.0 pmol/200 nL) or aCSF (200 nL) were performed over a 2-week period. This period was followed by a single challenge session, in which 0.3 pmol of salsolinol was microinjected to rats. Spontaneous activity was always monitored postinjection.. Intra-VTA salsolinol administration induces an increase of the spontaneous motor activity of the rats with the maximal effect at the dose of 30.0 pmol/200 nL. Salsolinol effects were blocked by the treatment with naltrexone or beta-FNA. Moreover, repeated injections of salsolinol produced locomotor sensitization.. Salsolinol induces locomotor activity and motor sensitization after intra-VTA administration. Moreover, the implication of the mu-opioid receptors was shown since the treatment with naltrexone or beta-FNA was able to suppress the salsolinol effects.

Topics: Animals; Dose-Response Relationship, Drug; Injections, Intraventricular; Isoquinolines; Male; Microinjections; Motor Activity; Naltrexone; Narcotic Antagonists; Rats; Rats, Wistar; Receptors, Opioid, mu; Ventral Tegmental Area