Effects of ageing on the behavioural responses to dopamine agonists: decreased yawning and locomotion, but increased stereotypy.
Sensorimotor function and the behavioural responses to a range of doses of subcutaneous apomorphine were assessed in mature (6-8 months) and old (23-26 months) Sprague-Dawley rats of comparable weight. In addition, the locomotor activity response of 12-month-old and 24-month-old rats to continuous infusions (14 days by osmotic minipump) of a selective dopamine D2 agonist. (+)-4-propyl-9-hydroxynaphthoxazine (PHNO, 10 micrograms/h) was investigated. Measures of spontaneous locomotor activity and motor coordination revealed impairments in the aged animals. Low doses of apomorphine (10-50 micrograms/kg), which preferentially activate dopamine autoreceptors, induced yawning, chewing mouth movements and penile grooming. The frequency of yawning and duration of penile grooming were significantly decreased in the old animals. In contrast, 200 micrograms/kg of apomorphine induced stereotyped sniffing and licking or gnawing, and these responses were significantly increased in the aged animals. There was a 25% decrease in striatal dopamine levels in the aged animals in this experiment. PHNO increased the amplitude of the circadian rhythms in locomotor activity exhibited by mature rats, and daytime tolerance to the stimulant effects of PHNO was reversed by stress in these animals. Both of these effects were attenuated in the aged rats. These findings suggest that (1) the dopamine receptors mediating yawning and stereotypy have different anatomical locations (2) ageing is associated with decreased responsiveness to stimulation of dopamine autoreceptors, consequent upon the loss of dopaminergic nerve terminals, and (3) while the functional response to selective stimulation of postsynaptic D2 receptors decreases with age, the postsynaptic response to a mixed D1/D2 agonist increases.
Stoessl
A J
AJ
Merck Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Harlow, Essex, U.K.
Martin-Iverson
M T
MT
Barth
T M
TM
Dourish
C T
CT
Iversen
S D
SD
D000375:Aging / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D015259:Dopamine Agents / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D010078:Oxazines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013239:Stereotyped Behavior / Q000187:drug effects / Q000502:physiology*; D015000:Yawning / Q000187:drug effects*
D015259:Dopamine Agents; D010078:Oxazines; C042631:naxagolide; D001058:Apomorphine