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Herberg and Montgomery (1987) recently described how behavioural factors can influence chlordiazepoxide (CDP) tolerance. Animals that received CDP before operant sessions showed tolerance to the sedative effect of CDP; the same treatment after operant sessions produced little tolerance. Such an effect is typically termed" Contingent" tolerance as tolerance is contingent upon animals receiving the drug in association with behavioural testing. Many studies indicate that contingent tolerance develops to a number of drugs in various behavioural and in vitro bioassays (Wolgin 1988). Collectively, the literature shows that for no single drug class have the necessary or sufficient conditions been established for tolerance to be behaviourally contingent (Goudie 1988). For example, there is much evidence that stimulants can show contingent tolerance in a variety of behavioural tests (Demellweek and Goudie 1983a, b) but there are also studies (e.g. Finnegan et al 1982) which report the development of tolerance to stimulants which was not behaviouraUy contingent.Herberg and Montgomery's (1987) data appear to contrust with our recent report (Gfiffiths and Goudie 1987) that tolerance to the sedative action of the benzodiazepine midazolam does not show a contingency effect. However, as noted by Herberg and Montgomery (1987), there were a number of procedural differences between these studies.
Herberg and Montgomery (1987) recently described how behavioural factors can influence chlordiazepoxide (CDP) tolerance. Animals that received CDP before operant sessions showed tolerance to the sedative effect of CDP; the same treatment after operant sessions produced little tolerance. Such an effect is typically termed" Contingent" tolerance as tolerance is contingent upon animals receiving the drug in association with behavioural testing. Many studies indicate that contingent tolerance develops to a number of drugs in various behavioural and in vitro bioassays (Wolgin 1988). Collectively, the literature shows that for no single drug class have the necessary or sufficient conditions been established for tolerance to be behaviourally contingent (Goudie 1988). For example, there is much evidence that stimulants can show contingent tolerance in a variety of behavioural tests (Demellweek and Goudie 1983a, b) but there are also studies (e.g. Finnegan et al 1982) which report the development of tolerance to stimulants which was not behaviouraUy contingent.Herberg and Montgomery's (1987) data appear to contrust with our recent report (Gfiffiths and Goudie 1987) that tolerance to the sedative action of the benzodiazepine midazolam does not show a contingency effect. However, as noted by Herberg and Montgomery (1987), there were a number of procedural differences between these studies.
Tolerance to the suppressive effects of cocaine on milk drinking by rats was studied using a contingent tolerance experimental design. Three separate groups (n = 6) of rats received 8.0, 16.0, or 32.0 mg/kg cocaine daily 15 min before a 15-min period of access to sweetened condensed milk for 20 days. Three additional groups of six rats each received the same chronic doses 15 min after access to milk. Milk, water, and food intake as well as body weight were measured daily. Tolerance effects were assessed by comparing initial acute dose-effect determinations with a probe dose-effect redetermination in which all rats again received doses of cocaine pre-session after having experienced the differential pre- or post-session chronic treatment. Behavioral tolerance on the milk intake measure was observed for the 8.0 mg/kg and 16.0 mg/kg doses, but not for the 32.0 mg/kg chronic treatment, even though the latter group exhibited evidence of tolerance in the water intake measure. Chronic treatment with 8.0 and 16.0 mg/kg produced different outcomes in that chronic exposure to 16.0 mg/kg in the presence of milk resulted in generalization of tolerance to both a lower (8.0 mg/kg) and a higher dose (32.0 mg/kg), but the group receiving 8.0 mg/kg did not exhibit generalization of tolerance to higher doses. Modest sensitization effects were observed in the rats treated post-session with either 8.0 or 16.0 mg/kg.(ABSTRACT TRUNCATED AT 250 WORDS)
The purpose of this study was to determine whether prior sensitization of stereotypy interferes with the development and retention of tolerance to amphetamine-induced hypophagia. Rats were given intermittent injections of either amphetamine (2.5 mg/kg) to induce sensitization of stereotypy, or saline. Subgroups from each group then received daily injections of either amphetamine (2 mg/kg) or saline and access to milk for 30 min. Both sensitized and nonsensitized groups became tolerant to drug-induced hypophagia at about the same rate and to about the same extent. Such tolerance was accompanied by a decrease in the frequency of stereotyped movements while milk was available. The rats were then given daily milk tests for 4 weeks without injections. Subsequent tests with amphetamine revealed that both groups lost tolerance to drug-induced hypophagia and displayed more intense stereotypy than they had prior to drug withdrawal. We conclude that sensitization of stereotypy produced by intermittent injections of amphetamine (2.5 mg/kg) does not retard the development of tolerance to drug-induced hypophagia and does not alter the rat's ability to suppress stereotyped movements. However, the loss of tolerance following drug withdrawal may have been due to the development of more intense stereotypy and/or the "unlearning" of previously acquired strategies for suppressing stereotypy.
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