TY - JOUR
T1 - Tolerance to N6-(l-phenylisopropyl) adenosine Contribution of behavioral mechanisms and cross-tolerance profile
AU - Spencer, D. G.
AU - Caldwell, P.
AU - Emmett-Oglesby, M. W.
N1 - Funding Information:
Acknowledgements-We thank Dr Harbans La1 and Dr John Lane for their conceptual and editorial contributions. This study was partially supported by grant number 82-l I-045 from the American Osteopathic Association.
PY - 1984/6
Y1 - 1984/6
N2 - The contribution of behavioral mechanisms to tolerance to N6-(l-rmphenylisopropyl)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 crosstolerant to the adenosine A1 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.
AB - The contribution of behavioral mechanisms to tolerance to N6-(l-rmphenylisopropyl)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 crosstolerant to the adenosine A1 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.
KW - N6-(l-phenylisopropyl)adenosine
KW - N6-cyclohexyl adenosine
KW - PIA
KW - behavior
KW - rats
KW - tolerance
UR - http://www.scopus.com/inward/record.url?scp=0021262418&partnerID=8YFLogxK
U2 - 10.1016/0028-3908(84)90149-7
DO - 10.1016/0028-3908(84)90149-7
M3 - Article
C2 - 6087187
AN - SCOPUS:0021262418
SN - 0028-3908
VL - 23
SP - 671
EP - 676
JO - Neuropharmacology
JF - Neuropharmacology
IS - 6
ER -