Biomedical subjects

R D Harland

Publications and source records attributed to R D Harland.

11 recordsLinked to original sources

PubMed1992

Tolerance to ethanol's effects on operant performance in rats: role of number and pattern of intoxicated practice opportunities.

Acquisition and retention of tolerance to ethanol's rate-decreasing effects on operant performance were examined in rats which received a 52-day regimen of ethanol or saline injections prior to and/or after each daily session. Eight groups of rats differed on: (a) number of days with intoxicated practice (pre-session ethanol); (b) intermittent (spaced) or daily (massed) intoxicated practice; and (c) post-session ethanol or saline on non-intoxicated practice days. Massed practice groups were given their presession saline days prior to their pre-session ethanol days. Ethanol dose-effect tests were given prior to, during, and after the chronic injection regimen. Under both spaced and massed practice conditions, the magnitude of tolerance developed increased directly with the number of pre-session ethanol days, even when absolute ethanol exposure was constant. No group showed complete tolerance loss. The post-session ethanol supplements (a) facilitated tolerance development in spaced practice groups and tolerance loss in massed practice groups, (b) blocked ethanol's low dose rate-increasing effects, and (c) produced an acute withdrawal-like performance disruption the next day. The results suggest that both intoxicated practice and practice during acute ethanol withdrawal influence the acquisition and retention of compensatory behaviors during ethanol tolerance development.

Alcoholic Intoxication↗

PubMed1989

Tolerance to ethanol's disruptive effects on operant behavior in rats.

The effects of pre-session and post-session daily ethanol injections on the development and loss of tolerance to ethanol's effects on fixed ratio operant performance in rats was assessed using a cumulative dosing procedure. Daily pre-session ethanol administration produced a greater decrease in ethanol sensitivity than did daily post-session ethanol. Both tolerance effects persisted for at least 1 month after the chronic injection phase. No changes in ethanol sensitivity were apparent in the saline control group and no changes in estimated blood ethanol levels were found after the chronic treatments. The post-session ethanol groups displayed a performance decrement during the initial segment of the chronic injection period, but improved significantly across the chronic phase. These data suggest that some delayed effect of ethanol initially impaired performance but that tolerance to this ethanol effect also occurred and probably contributed to the decline in ethanol sensitivity seen in these groups. Compensatory learning as the mechanism for tolerance development in the pre-session and post-session ethanol groups was supported by the finding of no change in ethanol sensitivity in rats exposed to comparable daily ethanol without any concurrent operant task on which the direct, immediate, or indirect, delayed ethanol effects could operate.

Animals↗

PubMed1989

Caffeine-phenylethylamine combinations mimic the cocaine discriminative cue.

Twelve male Sprague-Dawley rats were trained in a two-choice, food reinforced, drug discrimination task utilizing 10 mg/kg cocaine and saline as discriminative stimuli. Subjects were tested for stimulus generalization with a wide range of cocaine doses and several dose combinations of caffeine, ephedrine, and phenylpropanolamine (CEP). Caffeine produced only partial generalization. The triple CEP combinations resulted in complete generalization at high doses. All drugs produced response rate decrements at high doses. These data clearly indicate that certain look-alike stimulant products mimic the cocaine cue. The present data parallel human self-report data regarding the similarity in subjective profiles between illicit cocaine and the legal look-alike stimulants.

Animals↗

PubMed1989

Behavioral interaction between cocaine and caffeine: a drug discrimination analysis in rats.

The effects of caffeine upon the discriminative and rate-altering effects of cocaine were examined in rats. Using a food-reinforced two-lever operant procedure, 12 Sprague-Dawley male rats were trained to discriminate between 10 mg/kg cocaine and saline. Stimulus generalization tests with both cocaine and amphetamine resulted in a dose-related increase in cocaine-appropriate responding. A variable response rate topography was produced by cocaine. Caffeine also engendered a dose-related increase in cocaine-appropriate responding and resulted in a potency ratio of 15:1 when compared to cocaine. In contrast, increasing doses of caffeine produced a biphasic response rate function (first increases and then decreases). Response choice data suggested a potency relationship of amphetamine greater than cocaine greater than caffeine. Caffeine potentiated the discriminative stimulus properties of cocaine. Isobolographic analysis characterized this interaction as simple additivity. However, caffeine's effects upon the rate-altering effects of cocaine resulted in a biphasic interaction pattern. With low doses of cocaine in combination with various doses of caffeine, the interaction for rate reduction is best categorized as "supra-additive," in contrast, increasing either the cocaine dose or caffeine dose could change the interaction to simple additivity and/or infra-additivity.

Animals↗

PubMed1989

The discriminative stimulus properties of ethanol and acute ethanol withdrawal states in rats.

Twelve male Sprague-Dawley rats were trained in a standard two-choice Drug 1-Drug 2 discrimination task utilizing 3.0 mg/kg chlordiazepoxide (CDP, an anxiolytic drug) and 20 mg/kg pentylenetetrazol (PTZ, an anxiogenic drug) as discriminative stimuli under a VR 5-15 schedule of food reinforcement. Saline tests conducted at specific time points after acute high doses of ethanol (3.0 and 4.0 g/kg) indicated a delayed rebound effect, evidenced by a shift to PTZ-appropriate responding. Insofar as such a shift in lever selection indexes a delayed anxiety-like state, this acute 'withdrawal' reaction can be said to induce an affective state similar to that seen with chronic ethanol withdrawal states. Ethanol generalization tests: (1) resulted in a dose- and time-dependent biphasic generalization to CDP, (2) failed to block the PTZ stimulus and (3) failed to block the time- and dose-dependent elicitation of an ethanol-rebound effect. These data suggest that ethanol's anxiolytic effects are tenuous.

Affect↗

PubMed1988

The chlordiazepoxide/pentylenetetrazol discrimination: characterization of drug interactions and homeostatic responses to drug challenges.

Rats were trained to discriminate chlordiazepoxide (CDP) from pentylenetetrazol (PTZ) in a two-lever food motivated discrimination task. Training drug doses were adjusted until subjects emitted approximately 50% of their responses on each of the two drug-appropriate levers during saline injection tests. Tests that followed injection of CDP/PTZ combinations illustrated a reciprocal antagonism between the two drugs. Saline-injection tests that followed large dose injections of CDP revealed a period of predominantly PTZ-appropriate responding that persisted after the initial period of predominantly CDP-appropriate responding. These data are interpreted to suggest that, unlike some other drugs that have been shown to antagonize the behavioral and CNS effects of benzodiazepines, the interoceptive stimulus generated by PTZ occupies a position opposite to that of CDP along some single affective continuum. In addition, these data suggest that drug/drug (DD) discriminations are capable of characterizing the interactions between training drugs. Finally, the data suggest that the CDP/PTZ discrimination is a sensitive detector of bidirectional shifts in interoceptive stimulus state along the CDP/PTZ continuum.

Animals↗

PubMed1982