Tolerance to N6-(L-phenylisopropyl) adenosine. Contribution of behavioral mechanisms and cross-tolerance profile.
The contribution of behavioral mechanisms to tolerance to N6-(L-phenylisopropyl)adenosine (L-PIA) was studied, along with the degree of cross-tolerance to other drugs active in the CNS. Rats were stabilized on a fixed-ratio of a 20 lever-pressing schedule for food reward and were then assigned to three daily-treatment groups. One group (saline-behavior associated) was injected with saline 15 min before the session, another (L-PIA-behavior associated) was injected with L-PIA (0.08 mg/kg) 15 min before the session and the last (L-PIA-behavior dissociated) was injected with L-PIA (0.08 mg/kg) immediately after the session. Tolerance developed to the decreasing effects of L-PIA on response rate in both groups, L-PIA-behavior associated and L-PIA-behavior dissociated. Behavioral mechanisms were thus not important in tolerance to L-PIA. In subsequent cross-tolerance tests, L-PIA-tolerant rats were cross-tolerant to the adenosine Al receptor agonist, N6-cyclohexyladenosine. The drugs 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP), diazepam, pentobarbital, ketamine, clonidine, d-amphetamine and caffeine did not produce differential effects in L-PIA-tolerant and non-tolerant subjects; however, L-PIA-tolerant subjects were more sensitive to the suppressive effects of chlorpromazine on the response-rate.
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002110:Caffeine / Q000494:pharmacology; D002746:Chlorpromazine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D008297:Male; D010660:Phenylisopropyladenosine / Q000494:pharmacology*; D051381:Rats; D011956:Receptors, Cell Surface / Q000187:drug effects; D011963:Receptors, GABA-A; D011983:Receptors, Purinergic
D011956:Receptors, Cell Surface; D011963:Receptors, GABA-A; D011983:Receptors, Purinergic; D010660:Phenylisopropyladenosine; C027513:N(6)-cyclohexyladenosine; D002110:Caffeine; D000241:Adenosine; D002746:Chlorpromazine