Comparison of the discriminative stimulus function of ethanol following intracranial and systemic administration: evidence of a central mechanism.
Rats were trained using a two-lever drug discrimination procedure to press one lever following systemic administration of ethanol (1.0 mg/kg, IP) and another lever following IP injections of saline. After determination of an ethanol generalization curve (0.25-1.25 g/kg, IP), rats were surgically implanted with bilateral stainless steel guide cannulae that terminated in the lateral ventricles. Following surgery, the generalization curve was redetermined and did not differ from presurgery values. Then, generalization to bilateral intracerebroventricular (ICV) injections of ethanol (600.0 and 900.0 mM, 1.0 microliter/side) were administered alone and in combination with IP injections of ethanol. The ICV ethanol injections produced partial generalization, but the combination of ICV ethanol (600.0 and 900.0 mM) with IP ethanol (0.25 and 0.50 g/kg) injections were two- to threefold more potent then IP injections alone. Response rates were unaffected by any dose of ethanol tested. These data suggest central mediation of ethanol's discriminative stimulus function due to: 1) increased potency of systemically administered ethanol by centrally administered ethanol, and 2) partial generalization between centrally and peripherally administered ethanol.
Hodge
C W
CW
Department of Physiology and Pharmacology, Wake Forest University, Bowman Gray School of Medicine, Winston-Salem, NC 27157.
D000818:Animals; D001921:Brain / Q000033:anatomy & histology; D002490:Central Nervous System / Q000187:drug effects*; D004193:Discrimination Learning / Q000187:drug effects; D004192:Discrimination, Psychological / Q000187:drug effects*; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D005795:Generalization, Stimulus / Q000187:drug effects; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D008297:Male; D008845:Microinjections; D051381:Rats; D012055:Reinforcement Schedule
D000431:Ethanol