PubMed · 4730673
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S Bright, J Platano, J Jacobus. 1973-07-13. Amphetamine. Specific labeling and solution conformation.. https://doi.org/10.1021/jo00954a031
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Numerous studies have demonstrated that drugs of abuse activate the mesolimbic dopamine reward pathway, and it is widely held that this activation contributes to the motivational and positive reinforcing properties of these substances. However, there is evidence that endogenous opioid systems within this brain reward circuit also play a role in drug reinforcement and drug-seeking behavior. Using microdialysis in freely moving rats, we sought to determine whether various drugs of abuse (i.e., ethanol, cocaine, d-amphetamine, and nicotine) would increase neurotransmission of endogenous opioid peptides (i.e., endorphins) in the nucleus accumbens. Drugs were administered intraperitoneally twice at 3 h intervals, and the endorphin content of microdialysates was analyzed by a solid-phase radioimmunoassay. Acute administration of ethanol, cocaine, and d-amphetamine transiently elevated extracellular levels of endorphins in the nucleus accumbens, whereas nicotine and saline were without effect. We hypothesize that this drug-induced release of endorphins may contribute to the positive reinforcing and motivating properties of ethanol and psychostimulants.
We reported previously that environmental novelty enhances the acute psychomotor activating effects of amphetamine, its ability to induce behavioral sensitization, and its ability to induce c-fos mRNA in the striatum and other structures, relative to when amphetamine is given in the home cage. The purpose of the present experiment was 2-fold: to determine (1) whether environmental novelty has a similar effect on the ability of cocaine to induce c-fos mRNA, and (2) whether this effect is seen in neurologically-intact rats (in previous experiments we studied the intact hemisphere of rats with a unilateral 6-OHDA lesion). In the dorsal portion of the caudate putamen, core and shell of the nucleus accumbens, and in several cortical regions, both amphetamine (1.5 mg/kg) and cocaine (15 mg/kg) induced higher levels of c-fos mRNA expression when administered in a novel environment, relative to when they were administered in the home cage. The ability of environmental context to modulate psychostimulant drug-induced immediate early gene expression may be related to its ability to modulate forms of drug experience-dependent plasticity, such as behavioral sensitization.
Parkinson's disease is a neuropathological disorder involving the degeneration of dopamine neurons in the substantia nigra, with the resultant loss of their terminals in the striatum. This dopamine loss causes most of the motor disturbances associated with the disease. One animal model of Parkinson's disease involves destruction of the nigrostriatal pathway with a neurotoxin (6-hydroxydopamine) injected into this pathway. In unilaterally lesioned animals, injection of D-amphetamine causes rotation towards the lesioned side, while injection of apomorphine acting upon supersensitive postsynaptic dopamine receptors causes rotation away from the lesioned side. In this study, we tested the effects of acute and subchronic injection of a neurotensin analog (NT69L) on the rotational behavior induced by D-amphetamine (5 mg/kg) or apomorphine (600 microg/kg) in unilaterally 6-hydroxydopamine lesioned rats. Pretreatment of animals with intraperitoneal injections of NT69L (1 mg/kg) resulted in a significant reduction of apomorphine-induced contralateral rotation and D-amphetamine-induced ipsilateral rotation in these lesioned rats with an ED(50) of 40 and 80 microg/kg, respectively. After three daily injections of NT69L, its effects on this rotational behavior were unchanged, suggesting that no tolerance develops to this effect of NT69L.