ABSTRACT
RATIONALE: Drugs of abuse are initially used because of their rewarding properties. As a result of repeated drug exposure, sensitization to certain behavioral effects of drugs occurs, which may facilitate the development of addiction. Recent studies have implicated the metabotropic glutamate receptor 5 (mGlu5 receptor) in drug reward, but its role in sensitization is unclear. Stimulation of dopamine receptors plays an important role in drug reward, but not in the sensitizing properties of cocaine and morphine. OBJECTIVE: This study aims to evaluate the role of mGlu5 and dopamine receptors in the development of cocaine- and morphine-induced conditioned place preference (CPP) and psychomotor sensitization. MATERIALS AND METHODS: Rats were treated with the mGlu5 receptor antagonist MTEP (0, 1, 3, and 10 mg/kg, i.p.) or the dopamine receptor antagonist α-flupenthixol (0, 0.125, 0.25, and 0.5 mg/kg, i.p.) during place conditioning with either morphine (3 mg/kg, s.c.) or cocaine (15 mg/kg, i.p.). Furthermore, MTEP (1 mg/kg, i.p.) or α-flupenthixol (0.5 mg/kg, i.p.) was co-administered during cocaine (30 mg/kg, i.p.) or morphine (3.0 mg/kg, s.c.) pretreatment and psychomotor sensitization was tested 3 weeks post-treatment. RESULTS: MTEP attenuated the development of morphine- but not cocaine-induced CPP. In contrast, MTEP suppressed the development of cocaine- but not morphine-induced psychomotor sensitization. α-Flupenthixol blocked the development of both cocaine- and morphine-induced CPP but did not affect the development of sensitization to either drug. CONCLUSION: Dopamine receptor stimulation mediates cocaine and morphine reward but not sensitization. In contrast, the role of mGlu5 receptors in reward and sensitization is drug-specific.
Subject(s)
Behavior, Animal/drug effects , Cocaine/pharmacology , Morphine/pharmacology , Receptors, Metabotropic Glutamate/physiology , Reward , Animals , Dopamine Antagonists/pharmacology , Dose-Response Relationship, Drug , Flupenthixol/pharmacology , Male , Motor Activity/drug effects , Pyridines/pharmacology , Rats , Rats, Wistar , Receptor, Metabotropic Glutamate 5 , Receptors, Metabotropic Glutamate/antagonists & inhibitors , Thiazoles/pharmacologyABSTRACT
A high resolution (0.5 micrometer), two-dimensional microfluorimetric scanning procedure was used to quantitate the formaldehyde-induced fluorescence of noradrenaline in the iris of the rat. Scanning of large areas (50 x 50 micrometer) in the sympathetic innervated dilator muscle revealed an overlap between measurements of nerve fibers and of background (smooth muscle). In order to discriminate between both populations, the scan data were converted into fluorescence histograms (256 fluorescence classes, and subjected to mathematical analysis. The characteristics of the background histogram were obtained from scans of iris preparations devoid of fluorescent nerve fibers (pretreatment of the donor rat with reserpine or sympathetic denervation). A curve-fitting program was applied on those fluorescence classes in the normal iris histogram that represent measurements on pure background and resulted in a full background histogram. After subtraction of this background histogram from the original histogram, a nerve fiber histogram was obtained. The validity of the algorithm was evaluated by scanning iris preparations with varying background intensities. The results showed that quantification of the nerve fiber fluorescence was independent of variation in the background.
