Locomotor stimulant effects of acute and repeated intrategmental injections of salsolinol in rats: role of mu-opioid receptors

Abstract

Rationale: 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.

Objectives: 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.

Materials: 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.

Results: 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.

Conclusions: 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.