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


OBJECTIVE
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.


METHODS
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.
Hipólito
Lucía
L
Departament de Farmacia i Tecnología Farmacèutica, Universitat de València, Burjassot, Spain.
Sánchez-Catalán
María-José
MJ
Zornoza
Teodoro
T
Polache
Ana
A
Granero
Luis
L
D000818:Animals; D004305:Dose-Response Relationship, Drug; D007276:Injections, Intraventricular; D007546:Isoquinolines / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D008845:Microinjections; D009043:Motor Activity / Q000187:drug effects*; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017450:Receptors, Opioid, mu / Q000187:drug effects* / Q000378:metabolism; D017557:Ventral Tegmental Area / Q000378:metabolism
D007546:Isoquinolines; D009292:Narcotic Antagonists; D017450:Receptors, Opioid, mu; D009271:Naltrexone; C024524:beta-funaltrexamine; C036617:salsolinol