Effects of Δ1-tetrahydrocannabinol and food deprivation level on responding maintained by the opportunity to attack

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<ul><li><p>Physiology and Behavior, Vol. 9, pp. 795--800. Brain Research Publications Inc., 1972. Printed in U.S.A. </p><p>Effects of A - Tetrahydrocannabinol and Food Deprivation Level on Responding Maintained </p><p>by the Opportunity to Attack </p><p>D. R. CHEREK, 2 T. THOMPSON AND G. T. HEISTAD </p><p>Psychiatry Research Unit, Box 392 Mayo, University o f Minnesota Minneapolis, Minnesota 55455 </p><p>(Received 24 February 1972) </p><p>CHEREK, D. R., T. THOMPSON AND G. T. HEISTAD. Effects of A 1 -tetrahydrocannabinol and food deprivation level on responding maintained by the opportunity to attack. PHYSIOL. BEHAV. 9(5) 795-800, 1972.- Pigeons responded in a two key situation for food presentation and access to a restrained target bird that could be attacked. Doses of A ~ -tetrahydrocannabinol (0.125 and 0.25 mg/kg) which resulted in minimal changes in the rate of food reinforced responding, produced a marked suppression of attack responses and responding for target presentation, relative to their vehicle control rates. Manipulations of the level of food deprivation failed to mimic the effects of A'-tetra- hydrocannabinol. As the percent of frce-feeding weights of the birds was increased (5-10%) the rate of attack responses and responding for target presentation was unchanged or slightly increased, while the rate of food reinforced responding was decreased, in terms of percent change from the vehicle control rate. The selective suppressing effect of A'.tetrahydrocannabinol on attack rate and responding for target presentation does not appear to be due to a general depressant action of the drug or a change in the level of food deprivation. </p><p>Aggression A ~ -tetrahydrocannabinol Food deprivation Pigeon </p><p>IN EVALUATING the selective effect of a drug in reducing aggressive behavior, it is necessary to demonstrate that the effect does not merely represent a generalized depressant action (i.e., ataxia, impaired motor function, etc.). One method of dealing with this problem is to measure the effects of the drug on more than one behavior at the same or approximately the same times [21]. Previously, three studies have reported that crude marihuana extracts de- creased isolation-induced aggression in mice. In two of these studies [2, 19], the specificity of this effect could not be ascertained, since the effects of the drug on other behaviors were not determined. Santos, Sampaio, Fernandes and Carlini reported a decrease in aggression at doses of marihuana that produced no effects on motor activity [20]. These authors concluded that marihuana had a very selective effect of decreasing aggression. </p><p>In the present experiment, schedule-induced aggression in pigeons was used to evaluate the effect of ~l-tetra- hydrocannabinol. The monoterpenoid numbering system for tetrahydrocannabinols was employed. Delta-one- te t rahydrocannab ino l is equivalent to delta-nine- tetrahydrocannabinol using the pyran numbering system. </p><p>This technique had two advantages over the isolation- induced procedure in evaluating the effects of drugs on aggression. First, the method uses an objective automated recording of the aggressive behavior, thus avoiding the problems of reliability associated with the use of direct observational recording. Secondly, it is possible to compare the effects of delta-one-THC on two concurrently occurring behaviors, food reinforced responding and aggressive attack. The determination of selectivity of drug action on two behaviors occurring over the same time interval, within the same environmental context, affords a more valid estimate of the specificity of drug action. </p><p>EXPERIMENT 1 : EFFECTS OF DELTA-ONE-TETRAHY- DROCANNABINOL ON RESPONDING MAINTAINED BY </p><p>THE OPPORTUNITY TO ATTACK </p><p>METHOD </p><p>Animals </p><p>Six experimentally naive male White Carneaux pigeons </p><p>~This research was supported by U.S.P.H.S. grant MH-08565. 2 Reprints may be obtained from D. R. Cherek, Research Department, Kalamazoo State Hospital, Kalamazoo, Michigan 49001. Basic data </p><p>tables may be obtained from D. R. Cherek upon request. </p><p>795 </p></li><li><p>796 CHEREK, THOMPSON AND HEISTAD </p><p>(Palmetto, Sumter, So. Carolina) 6 -12 months old were used. Three pigeons served as experimental birds, and three as target birds. The experimental birds were food deprived and maintained at 80% of their free feeding weights. Target birds were not food deprived. Each target bird was paired with a specific bird for the entire experiment. All pigeons were housed in individual cages with water continuously available. </p><p>Apparatus </p><p>The experimental apparatus was a standard pigeon test chamber (LeHigh Valley Electronics), containing two re- sponse keys and a solenoid operated food delivery mechanism. The response keys were illuminated by white lamps; the chamber contained an overhead light. </p><p>The apparatus for recording aggressive attack was very similar to that described by Azrin, Hutchinson and Hake [1]. The target birds were restrained in a box by metal bands fastened over each wing. The restraining box was mounted on a metal frame containing an adjustable spring and microswitch. A force of at least 100 g exerted against the front of this box by the experimental bird, during periods of attack, resulted in a switch closure. Each switch closure was recorded as an attack response. The restraining box was located on the side of the chamber. Plexiglas shields on either side of the restraining box prevented the experimental pigeon from getting behind the target, since only displacements of the front of the box were recorded. Although the target birds made vigorous defensive move- ments prior to attack episodes, such movements, by themselves, failed to activate the microswitch. </p><p>Procedure </p><p>Schedules. Responding on the right (food) key resulted in the presentation of food (Purina poultry pellets) for 3 sec. Access to food was presented on a response-initiated fixed-interval (FI) 2 min schedule [17]. On such a schedule, the first response (at the beginning of the session or following food presentation within the session) initiated a 2 min interval, and the first response after the interval elapsed resulted in food presentation. This schedule has been found to induce aggression in pigeons [4], and the highest rates of responding for the opportunity to attack and of attack responses were observed at an FI value of 2 or 3 min [6]. </p><p>Responding on the left (target) key on a fixed-ratio (FR) 2 schedule (i.e., two responses) resulted in access to a live target bird that could be attacked. A transparent Plexiglas shield, positioned in front of the target bird, prevented the experimental bird from gaining access to the target bird. In the original description of the apparatus [ 1 ], a shield was not used, thus allowing the experimental bird continual access to the target bird throughout the session. Responding on the target key produced a 3 sec tone, and activated a motor driven shaft that pulled the shield to one side, exposing the target bird. The shield remained in the open position for 15 sec, and then was closed by a second activation of the motor. During the time that the target bird was accessible, the light on the target key was extinguished, and the responses on that key were of no consequence. </p><p>To ensure that responding for access to the target bird was not maintained by superstitious food reinforcement (i.e., an accidental correlation of food presentation with </p><p>responding on the target key): (a) a 15 sec change over delay (COD) was interposed between the occurrence of each response on the target key and the presentation of food following a response on the food key [3] ; and, (b) a 15 sec protective contingency between the termination of target availability (the returning of the shield in front of the target bird) and the presentation of food following a response on the food key. This prevented the accidental temporal association of responding on the target key or movement of the shield with access to food. </p><p>Drug. Synthetic delta-one-THC in 95% ethanol (200/mg/cc) was suspended in a mixture of Arlacel-20 and Tween-65 in saline [18]. Suspensions were stored in the dark at 4C. Doses of 0.125, 0.25, 0.5, and 1.0 mg/kg of delta-one-THC were administered in a random order, with each dose being given twice. Pigeons were injected I. M. with vehicle or delta-one-THC suspension in a constant volume of 1 ml/kg of body weight two hr prior to the beginning of the session. Six days elapsed between each drug session to minimize the development of tolerance [16]. </p><p>Training. Birds were hand shaped to key peck for food on a FR 1 schedule. An FI 5 sec schedule was then instituted, and over sessions, the value of the FI was increased to 2 min. Pigeons were run on the FI 2 min food reinforcement schedule until the rate of responding stabilized (approx- imately 2 weeks). During this initial training, the target key was covered and the restraining box was absent. Following stabilization of food reinforced responding, the target was placed in the restraining box, and the target key was uncovered and illuminated. For three consecutive sessions, a single response (FR 1) on the target key resulted in access to the target bird. After the third session, two responses (FR 2) on the target key were required to gain access to the target bird. Pigeons were run on the FI 2 rain (food) FR 2 (access to the target bird) schedules for ten 45 rain daily sessions. </p><p>Following this training phase, birds were given the opportunity to respond for access to the target bird on every third session. During other intervening sessions, the pigeons were run on the FI 2 min food schedule alone, with the target bird and restraining box absent. Pigeons were not given access to the target bird on each session: (a) to minimize injury to the target; and, (b) to avoid the decrease in aggression sometimes observed when birds are exposed to a live target bird over successive sessions [5]. Vehicle or delta-one-THC injections were also given every third session, when the target bird was present (see Table 1). Drug sessions were run every 6 days, with one vehicle control session run before and after each drug session. </p><p>RESULTS </p><p>A'-Tetrahydrocannabinol produced a dose-dependent decrease in responding on the FI 2 min food reinforcement schedule. The slight decrease in response rate observed at 0.125 and 0.25 mg/kg of delta-one-THC, was primarily the result of increased postreinforcement pausing (i.e., the time between food presentation and the initiation of the next fixed interval). Higher doses of delta-one-THC (0.5 and 1.0 mg/kg) resulted in further increases in pausing, or a complete cessation of responding after birds had responded through some intervals early in the session. There was very little effect on the temporal patterning of responding, </p></li><li><p>~1 -THC, FOOD DEPRIVATION AND AGGRESSION 797 </p><p>TABLE 1 </p><p>EXPERIMENTAL DESIGN FOR EXPERIMENTS 1 AND 2 </p><p>Exp. 1 Exp. 2 Session Schedule(s) Target Drug % body weight </p><p>1 FI 2 min (food) absent no 80 </p><p>2 FI 2 min (food) absent no 80 </p><p>3 FI 2 min (food); FR 2 (target) present vehicle 80 (control) </p><p>4 FI 2 min (food) absent no 80 </p><p>5 FI 2 min (food) absent no 80 </p><p>6 FI 2 min (food) FR 2 (target) present THC 85, 90, or 100 </p><p>(experimental) </p><p>7 sequence repeated </p><p>except at the highest dose (1.0 mg/kg). Similar results have been reported for pigeons responding on fixed ratio and fixed intervals reinforcement schedules following the administration of delta-one-THC [ 14 ]. </p><p>The effects of delta-one-THC on the overall mean response rate on the FI 2 min (food) and FR 2 (target presentation) schedules are shown in Fig. 1. At 1.0 mg/kg, both rates of responding decreased to between 0-20% of the control (vehicle) rate in pigeons P 51 and P 52; with pigeon P 50 the rate of food reinforced responding decreased to 30% of control, and the response rate for target presentation decreased to less than 10% of the control rate. All other doses of delta-one-THC resulted in suppression of responding for target presentation more than the rate of responding for food presentation, relative to their vehicle control rates. This effect is most evident at 0.125 mg/kg of delta-one-THC, where there was little or no effect (95-110% of control rate) on food responding, while the rate of responding for target presentation was decreased to 50-60% of the vehicle control rate. Similarly, at 0.25 and 0.5 mg/kg of delta-one-THC the decrease in food responding (75-90% and 40-55% of control rate) was substantially less than the observed decrease in the rate of responding for target presentation (25-50 and 0-20% of the control rate). </p><p>The effects of delta-one-THC on the mean number of target and food presentations per session are shown in Table 2. Low doses of delta-one-THC (0.125 and 0.25 mg/kg) resulted in marked decreases in the number of target presentations, while having little or no effect on the number of food presentations. Higher doses of delta-one-THC (0.5 and 1.0 mg/kg) decreased the number of target and food presentations, with the number of target presentations being decreased more than the number of food presentations at both dosage levels. reinforced responding, produced a marked decrement in the rate of attack responses (15-60% of the control rate). Both the rate of responding for target presentation and the rate </p><p>14o </p><p>Ld </p><p>-J 0 n.. l- z o u i..i. o </p><p>zSO I..I..I O. </p><p>Food </p><p>0--,,,0 </p><p>R50 RSI R~ </p><p>, </p><p> . , </p><p>,, "{~, ', ,, ,, \ ,, ', "~; </p><p>"-.~ \ QI25Q25 0.5 tO 0125025 Q5 tO 0.125025 0.5 tO </p><p>A"-TETRAHYDROCANNABINOL mg/kg </p><p>FIG. 1. The effects of delta-one-THC on the mean response rate on the FI 2 min (food) and FR 2 (target presentation) schedules. The verticle lines labeled F (food responding) and T (responding for target presentation), represent the range of response rates observed during vehicle control sessions expressed as a percentage of the mean control value. The mean response rates (vehicle controls) for food responding were: 30.31 (P 50),41.92 (P 51), and 34.98 (P 52); responding for target presentation were: 0.74 (P 50), 0.60 (P 51), and 0.66 (P 52) responses per minute. The verticle lines at each </p><p>dosage point represent the range of two observations. </p><p>of attack responses are similarly affected by delta-one-THC, with the rate of attacks being suppressed more at a given dose of delta-one-THC (relative to control rate) than the rate of responding for food presentation. </p><p>EXPERIMENT 2: EFFECTS OF FOOD DEPRIVATION LEVEL ON RESPONDING MAINTAINED BY THE </p><p>OPPORTUNITY TO ATTACK </p><p>Falk has proposed that schedule-induced aggression, schedule-induced escape, and polydipsia be included in a new class of behaviors termed "adjunctive" [11]. This classification is based upon common properties and similar functional relationships to a number of variables reported for these behaviors. </p><p>The level of food deprivation has been shown to be an important determinant of schedule-induced or adjunctive behaviors. Schedule-induced polydipsia and airlicking are decreased following decreases in the level of food depri- vation [7, 10...</p></li></ul>