Peptides, Vol. 12, pp. 1-5. ©PergamonPress plc, 1991.Printedin the U.S.A.

0196-9781/91 $3.00 + .00

Effects of DDAVP on Movement Planning and Execution Processes in Healthy Young Adults JOHN S. CARTER, HARRIET G. WILLIAMS, J. M A R K DAVIS, RICHARD A. R O T r E R AND MARY E. CLANCY

Department of Exercise Science, University of South Carolina, Columbia, SC 29208 Received 8 August 1990

CARTER, J. S., H. G. WILLIAMS,J. M. DAVIS, R. A. ROTrER AND M. E. CLANCY. Effects of DDAVP on raoveraentplanning and execution processes in healthy young adults. PEPTIDES 12(1) 1-5, 1991.--This study investigatedthe effects of an acute dose of DDAVP on speed and consistencyof planning and execution of simple and complex movements in healthy young adults. A simplereaction time task (SRT), a simple movementtask (SMT), and a complex movementtask (CMT) were performed with and without a 0.6 ml intranasaldose (60 p.g) of DDAVP. Results indicatedDDAVP-treated individualsplanned and executed CMT and SRT tasks faster and more consistentlythan did placebo-treated subjects. There were nonsignificantDDAVP effects on speed and variabilityof both RT and MT processes involvedin the SMT. Behavior

DDAVP

Desmopressin

Motor

Movement

ARGININE vasopressin (AVP) is formed by neural cells in hypothalamic nuclei, synthesized in magnocellular neurons of the hypothalamus, and stored in the neurohypophysis (13). 1-Desamino-8-D-arginine vasopressin (DDAVP), one of the synthetic analogs of AVP, is used in antidiuretic replacement therapy to manage diabetes insipidus and to alleviate temporary polydipsia and polyuria following head trauma or surgery in the pituitary region (1). AVP appears to be transported across the blood-brain barrier to act directly on the central nervous system (CNS) as well as to facilitate neural activity in limbic, midbraln, and forebrain areas, structures known to be linked with memory processes, cognitive function, and learning in humans (2, 11, 20, 34, 35). There is nearly unanimous agreement that AVP/AVP analogs affect cognitive functioning, memory processes, and learning in a positive way in humans (12, 29, 30). Significant improvements have been shown with vasopressin treatment in a variety of learning (concept shift, serial learning, arithmetic, and passive avoidante) tasks and memory (memory for implicational sentences, free recall, semantically related words, and visual sequential memory) tasks (2--6, 32). Enhancement of attention, concentration, mood, and self-confidence has also been found to accompany treatment with AVP/AVP analogs (15-17, 21, 22, 33, 36, 37). There are important links between CNS function and performance of skilled motor acts. Most motor activities require planning of action sequences in advance of actual performance. The CNS is believed to regulate movement by organizing complex series of movements into motor programs which are centrally stored, structured in advance and, when activated, "run off" with or without peripheral feedback (25,27). Reaction time (RT) involves CNS processes, and by definition, RT is the time from the

Reaction

appearance of a sudden and unanticipated signal to the beginning of a volitional motor response. RT includes the time taken for such cognitive-related events as stimulus identification, decisionmaking, response selection and programming. RT is slowed when there is an increase in the number or complexity of movements to be performed (8-10), and this slowing is thought to be due to increased time required to plan or program additional components of movements (27). Since AVP/AVP analogs appear to affect cognitive functions of the CNS in a convincing manner, it seems logical that they may also facilitate neural motor control processes involved in planning and executing overt motor acts. Little if any attention has been given to the potential facilitory effects of AVP or DDAVP on motor functions. The purpose of this study was to investigate the effects of an acute dose of DDAVP on the speed and consistency of planning and execution of simple and complex movements in healthy young adults. METHOD

Subjects

Participants in the study were twenty-four healthy, consenting volunteers (23 males, 1 female) from metropolitan Columbia, SC. The average age of subjects was 24 years (range= 19-32 years). None of the participants had any physical or emotional impairment which would interfere with normal motor performance; none were on medication. All subjects were nonsmokers and had resting blood pressures below 140/90 mmHg and resting heart rates less than 85 bpm.

Tasks Participants were asked to complete three tasks: a simple re-

2

action time task (SRT), a simple movement task (SMT), and a complex movement task (CMT). A Lafayette Reaction/Movement Timer Model 63017 was used to record reaction time (RT) and movement time (MT). Each subject completed 15 trials on each task, a total of 45 trials per session; however, only data from the latter 10 trials were analyzed in order to avoid warmup effects. All tasks were presented in a predetermined random order. Simple reaction time (SRT). Individuals were seated facing a motor sequencing apparatus with a warning/stimulus light placed on the top center. Two telegraph keys were located in front of the apparatus, one to the left and one to the right. Subjects depressed the left telegraph key with the index and third fingers of the dominant hand. After a randomized 1-, 2-, or 3-second forewarning period (signaled by a white light), a red stimulus light appeared. The subject responded to the stimulus light by lifting the fingers as quickly as possible. Simple movement task (SMT). Procedures were similar to those for SRT; however, on the appearance of the red stimulus light, the subject lifted the fingers from the left telegraph key and moved them as quickly as possible to depress the right telegraph key located at a distance of 60.96 cm. Complex movement task (CMT). After a randomized 1-, 2-, or 3-second foreperiod, one of three different stimulus lights appeared (red, green, or blue). Each stimulus light was associated with a different movement sequence which involved five fine distal control actions: flipping of 2 toggle switches, depressing a small lever, rotating a small knob, pushing a small knob, and squeezing a grip handle. Upon stimulus onset, the subject lifted the fingers from the left telegraph key, performed the appropriate movement sequence, and depressed the right telegraph key. Presentation of movement sequences was randomized across subjects.

Experimental Conditions All tasks were performed with and without DDAVP. Individuals were randomly assigned to one of two treatment groups (n = 12): 1) a drug-placebo group (D-P) in which tasks were performed with DDAVP in Session 1 and placebo in Session 2; and 2) a placebo-drug group (P-D) in which tasks were performed with placebo in Session 1 and DDAVP in Session 2. The two testing sessions were separated by 4--7 days and all sessions were held between 1300 and 1800 hours.

Procedures Each subject received either a 0.6 ml dosage (60 Ixg) of DDAVP in a sterile aqueous solution of cholobutanol, sodium chloride, and hydrochloric acid, or an equal volume of saline (placebo) administered intranasally. A double-blind procedure was utilized. Although this test dosage was approximately three times that recommended for adults with diabetes insipidus, both dosage and route of administration were consistent with that used in previous studies and are considered both safe and effective (1, 2-4, 6, 14, 31). DDAVP is typically absorbed into the bloodstream with peak plasma levels reached within 30-50 minutes after administration. This dosage has a biological effect which lasts 8-12 hours, followed by a gradual loss in effectiveness over an additional 12hour period. Biphasic half-lives of DDAVP are 7.8 and 75.5 minutes for fast and slow phases; plasma half-life ranges between 2.8-3.6 hours (18, 19, 24, 28). Prior to treatment administration, participants were seated and given preliminary blood pressure and resting heart rate checks. Individuals were excluded from the study if blood pressure ex-

CARTER ET A L

TABLE 1 AVERAGE SPEED AND VARIABILITY OF PERFORMANCE: MEANS AND (STANDARD ERRORS) IN MILLISECONDS

Speed of Performance Reaction Time (RT)

Movement Time (MT)

Task

DDAVP

Placebo

DDAVP

Placebo

SRT SMT CMT

228 (005) 265 (007) 555 (083)

239 (006) 268 (006) 591 (098)

353 (014) 4441 (169)

360 (022) 4579 (163)

Variability of Performance RT Variability

MT Variability

Task

DDAVP

Placebo

DDAVP

Placebo

SRT

024 (002)

039 (005)

SMT

003 (004)

031 (003)

037 (006)

102 (063)

CMT

123 (030)

155 (042)

463 (042)

517 (081)

SRT = simple reaction time. SMT = simple movement task. CMT = complex movement task. ceeded 140/90 mmHg or resting heart rate was greater than 85 bpm. Subjects rested in a supine position on a padded table, and a premeasured amount of DDAVP or placebo was administered intranasally by the investigator. Care was taken to insure that none of the dosage entered the throat or was swallowed. Subjects remained supine for 15-20 minutes to allow absorption of DDAVP into the system. A second blood pressure and heart rate check was taken at 20 minutes; testing began immediately following this check. A third hemodynamic check was performed at the completion of the testing session. No significant changes in either heart rate or blood pressure were observed during or at the conclusion of testing.

Research Design and Statistical Analysis The design of the study was a 2 (Treatment Group) x 2 (Movement Task) x 2 (Session) factorial with repeated measures on the last two factors. Separate repeated measures MANOVAs with appropriate follow-up tests were used to analyze each of four dependent variables: mean RT and MT, and variability of RT and MT. SRT performances were analyzed using a 2 (Treatment Group) x 2 (Session) repeated measures ANOVA. RESULTS

Means and standard errors of RT and MT (10 trials) for each task are shown in Table 1.

Speed of Reaction Simple reaction time. Significant main effects were found for Group [Hotelling-Lawley Trace, F(1,22)=5.52, p