Pharmacology of drug self-administration.
Limited access to drugs provides a reliable model for their acute-reinforcing effects and a means by which to explore neuropharmacological mechanisms involved in these effects. In limited access situations intravenous self-administration rates of opiates and psychomotor stimulants is inversely related to dose, and competitive antagonists at low doses increase the number of injections self-administered. Competitive agonists decrease drug self-administration. However noncompetitive antagonists tend to produce decreases in self-administration and the specificity of these results are difficult to interpret. A limited access procedure of ethanol (10% v/v) self-administration using a sucrose or saccharin fade out procedure resulted in reliable and stable ethanol (10% v/v) and water self-administration in a concurrent choice situation using nondeprived unselected Wistar and alcohol preferring P-rats. As observed by others, the opiate antagonist naloxone decreased fluid intake in both strain of rats. However, contrary to earlier results naloxone did not produce a selective decrease in ethanol preference. The serotonin antagonist methysergide had no significant effect on fluid intake or ethanol preference. However, the long-acting dopamine agonist bromocriptine decreased ethanol intake and increased water intake producing a significant decrease in ethanol preference. The results with naloxone suggest that opiate interactions with ethanol may reflect a more general effect on consummatory behavior and the results with bromocriptine suggest that the reinforcing effects of low doses of ethanol may involve a dopaminergic component. Future studies should explore further the interactions of ethanol with competitive antagonists (if possible), and fluid intake or ethanol preference with limbic-extrapyramidal circuitry involved in mediating the reinforcing actions of other drugs of abuse.
Koob
G F
GF
Research Institute of Scripps Clinic, Department of Neuropharmacology, La Jolla, CA 92037.
Weiss
F
F
D000818:Animals; D015259:Dopamine Agents / Q000494:pharmacology; D018492:Dopamine Antagonists; D006801:Humans; D011619:Psychotropic Drugs / Q000494:pharmacology; D012646:Self Administration / Q000523:psychology*; D012702:Serotonin Antagonists / Q000494:pharmacology
D015259:Dopamine Agents; D018492:Dopamine Antagonists; D011619:Psychotropic Drugs; D012702:Serotonin Antagonists