Pharmacological Research Communications, VoL 20, No. 12, 1988 1101

PROLACTIN AFFECTS CENTRAL DOPAMINE RECEPTOR FUNCTION: THE BEHAVIORAL

MODEL OF AGED RATS

Filippo Drago, Francesco Spadaro and Umberto Scapagnini

Institute of Pharmacology, University of Catania Medical School, I ta ly.

Besides the expression of animal behavior, prolactin affects a variety

of neurochemical parameters. A correlation may be demonstrated between

the influence of this hormone on central dopamine neurotransmission and

its effects on motor act ivi ty (Drago et al . , 1984). As an example, high

levels of plasma prolactin are associated with a potentiation of

amphetamine- or apomorphine-induced stereotypies, and a reduction of

haloperidol-induced catalepsy (Drago et a]., 1981). An interesting

prob]em was raised concerning the possibi] i ty that pro]actin may be

involved in dopamine receptor upregu]ation induced by haloperidol or

estrogen treatment. Indeed, a substantial increase in striata! D2

receptors has been shown following chronic prolactin administration.

This finding has recently been extended also to aged rats that show a

dramatic increase in str iatal spiperone binding after chronic prolactin

administration (Levin et a]., 1983). As str iatal dopamine receptor

downregulation has been involved in many behavioral disturbances of aged

rats, their improvement would be expected in animals bearing high levels

of plasma prolactin (Joseph et aI., 1986).

The model of hyperprolactinemia induced by pituitary homografts under

the kidney capsule has mainly been used in these experiments. This model

has been selected as being able to avoid the administration of

heterologous prolactin. Alternatively, chronic rat prolactin

administration via permanently implanted subcutaneous minipumps was

used.

Aged rats of the Sprague-Dowley strain were tested in a battery of

behavioral tasks including open f ield and rotorod tests, Y maze,

0031-6989/88/121101-2/S03.00/0 �9 1988 The Italian Pharmacological Society

1102 Pharmacological Research Communications, VoL 20, No. 12, 1988

constrained swim, acquisition and retention of active avoidance

behavior. In al l these behavioral tasks, aged rats exhibited a

performance !eve! lower than that of younger animals. Hyperprolactinemia

induced either by p i tu i tary homografts or by chronic administration of

rat prolactin was followed by an overa!I improvement of behavioral

def ic i t of aged rats. This improvement appeared to be more marked for

pure moto r tasks (rotorod, ambulation in open f ie ld ) , than for

motivational!y-oriented behaviors (Y maze, constrained swim, avoidance

behavior).

These findings suggest that prolactin modulates st r ia taI dopamine

neurotransmission in ageing. Since moderate hyperprolactinemia is a

common finding in aged rats, i t remains to be elucidated why behaviora!

def ic i ts are present in these animals despite of the high leves of

plasma prolactin levels. To answer to this question an experiment was

carried out with aged rats bearing p i tu i tary homografts obtained from

age-matched animals. No change was found in this case in the behaviora!

alterations of aged rats, although they exhibited a further increase in

plasma prolactin levels. This suggests that proIactin secreted in aged

animals may be biological ly inactive.

REFERENCES

- Drago, F., J .M. van Ree, B. Bohus and D. de Wied (1981) Eur. J.

PharmacoI. 72:249-254.

- Drago, F., G. Pennis!, U. Scapagnini (1984) In: Pi tui tary

Hyperfunction: Physiopathology and Clinical Aspects, edited by F.

Camanni and E.E. Muller, New York: Raven Press, pp. 315-320.

- Joseph, J.A., G.S. Roth and A.S. Lippa (1986) Neurobiol. Aging

7:31-37.

Levin, P., J.K. Janda, J.A. Joseph and G.S. Roth (1983). Life Sci.

32:1743-1749.