European Journal of Pharmacology, 42 (1977) 191--192
191
© Elsevier/North-Holland Biomedical Press
Rapid communication ~-ENDORPHIN AND MALE SEXUAL B E H A V I O R BENGT J. MEYERSON* and LARS TERENIUS
Department of Medical Pharmacology, University of Uppsala, Sweden Received 18 January 1977, accepted 18 January 1977
It was recently reported that ~-endorphin (~-LPH61.91) injected intraventricularly (20-40 gg) or intracerebrally (4 #g) into rats induced rigid immobility suggesting the induction of a cataleptic state (Bloom et al., 1976; Jacquet and Marks, 1976). In c o m m o n with ACTH, ~-MSH and morphine, low doses (0.01 --0.3 ug) of/~-endorphin have been reported to induce excessive grooming behavior in rats (Gispen et al., 1976). In the present communication we report on the effects of ~-endorphin on copulatory behavior in male rats. Intact male Wistar rats (350--400 g) were exposed to estrous females at 2--3 days' interval for 6 weeks before the peptide treatment started. At this time all males initiated mounting of the stimulus female within 5 sec. At least 4 w e e k s before /~-endorphin injection both lateral ventricles were cannulated. The peptide was injected bilaterally over a 5 min period in a total volume of 25 #l artificial CSF or saline. After peptide injection, the rat was placed in an observation cage and allowed to adapt for 5 rain. The exploratory behavior during this time was measured by an "Animex" activity meter placed under the observation cage. After this period a castrated male rat was let into the cage and the socio-sexual interaction scored. The castrated male was replaced after 5 min b y an ovariectomized rat displaying intense estrous behavior (induced by estradiol benzoate, 25 pg/kg, and progesterone, 1 mg/rat; the hormones given 48 h apart *Present address: Department of Medical Pharmacology, University of Uppsala, Box 573, Biomedicum, S-751 23, Sweden.
and the female used 4--6 h after progesterone injection). Each male was allowed 10 min with a stimulus female when m o u n t latency and number of mounts were measured. Most males were used in more than one treatment category. At least one drug-free test was allowed b e t w e e n tests with ~-endorphin to assure that the copulatory response was at the pre-experimental level, The exploratory activity in the observation cage was n o t influenced by 1 gg but slightly reduced by 3 ~g ~-endorphin. The scores for socio-sexual approach towards the castrated male ,were no different from those of control animals. When an estrous female was used as a stimulus animal the 1 ~g ~-endorphin-treated males investigated the anogenital area of the female very actively and pursued her. However, only five o u t of thirteen males initiated mounting (statistically different from the controls. Fisher exact probability test, p < 0.016. The treated male repeatedly approached the female and displayed all items of the precopulatory repertoire b u t interrupted the performance just when he normally should have m o u n t e d the female. Those males who initiated mounting had a longer latency and a low m o u n t frequency compared to controls (table 1). Mounting was also performed in an abnormal way (no real clasp and thrust) so hardly any intromissions were achieved. We could see no evidence of muscular rigidity or signs of a cataleptoid state at the 1 pg dose level. On the contrary, the animals were very active. After 3 #g/~-endorphin, the frequency of pur-
192
suit decreased and after 30/~g we could confirm the cataleptoid state described by Bloom et al. (1976) and Jacquet and Marks (1976).
TABLE 1 Mounting behavior in intact male rats after intraventricular injection of ~-endorphin. Treatment
No.
Total
None 16 CSF, saline 14 ~-Endorphin 1 ~g 13 5-Endorphin 3 #g 6 Naltrexone 1 mg/kg 9 Naltrexone 1 mg/kg and -endorphin 1 ~g 8
Mounting behavior Mounting
Lattency (sec) 1
Frequency (mounts, min -l)
16 14
< 5 < 5
4.0 5.0
5
35
2.12
1
10
1.12
9
< 5
3.2
8
< 5
5.0
The effect of 1 pg/~-endorphin could be prevented by the opiate antagonist naltrexone given subcutaneously 30 min before the peptide (table 1), suggesting that the effect was induced via opiate receptors. Our data describe an effect of ~-endorphin on a behavioural pattern which is a constituent of the normal repertoire of the animal. They strengthen the hypothesis (Bloom et al., 1976), that changes in ~-lipotropin-endorphin homeostasis can cause profound behavioural changes. The ~-endorphin was purchased from Peninsula Labs, San Carlos, California, while naltrexone was donated by Endo Labs, Garden City, N.Y. The work was supported by the Swedish Medical Research Council.
References
1Median values. 2 W h e n r e t e s t e d 3 h after the ~-endorphin injection,
all animals m o u n t e d with a latency < 5 and frequency 4.5.
Bloom, F., D. Segal, N. Ling and R. Guillemin, 1976, Endorphins: profound behavioral effects in rats suggest new etiological factors in mental illness, Science 194,630. Gispen, W.H., V.M. Wiegant, A.F. Bradbury, E.C. Hulme, D.G. Smyth, C.R. Snell and De Wied, 1976, Induction of excessive grooming in the rat fragments of lipotropin, Nature 264, 794. Jacquet, Y.F. and N. Marks, 1976, The C-fragment of ~-lipotropin: An endogenous neuroleptic or antipsychotogen?, Science 194,632.
191
© Elsevier/North-Holland Biomedical Press
Rapid communication ~-ENDORPHIN AND MALE SEXUAL B E H A V I O R BENGT J. MEYERSON* and LARS TERENIUS
Department of Medical Pharmacology, University of Uppsala, Sweden Received 18 January 1977, accepted 18 January 1977
It was recently reported that ~-endorphin (~-LPH61.91) injected intraventricularly (20-40 gg) or intracerebrally (4 #g) into rats induced rigid immobility suggesting the induction of a cataleptic state (Bloom et al., 1976; Jacquet and Marks, 1976). In c o m m o n with ACTH, ~-MSH and morphine, low doses (0.01 --0.3 ug) of/~-endorphin have been reported to induce excessive grooming behavior in rats (Gispen et al., 1976). In the present communication we report on the effects of ~-endorphin on copulatory behavior in male rats. Intact male Wistar rats (350--400 g) were exposed to estrous females at 2--3 days' interval for 6 weeks before the peptide treatment started. At this time all males initiated mounting of the stimulus female within 5 sec. At least 4 w e e k s before /~-endorphin injection both lateral ventricles were cannulated. The peptide was injected bilaterally over a 5 min period in a total volume of 25 #l artificial CSF or saline. After peptide injection, the rat was placed in an observation cage and allowed to adapt for 5 rain. The exploratory behavior during this time was measured by an "Animex" activity meter placed under the observation cage. After this period a castrated male rat was let into the cage and the socio-sexual interaction scored. The castrated male was replaced after 5 min b y an ovariectomized rat displaying intense estrous behavior (induced by estradiol benzoate, 25 pg/kg, and progesterone, 1 mg/rat; the hormones given 48 h apart *Present address: Department of Medical Pharmacology, University of Uppsala, Box 573, Biomedicum, S-751 23, Sweden.
and the female used 4--6 h after progesterone injection). Each male was allowed 10 min with a stimulus female when m o u n t latency and number of mounts were measured. Most males were used in more than one treatment category. At least one drug-free test was allowed b e t w e e n tests with ~-endorphin to assure that the copulatory response was at the pre-experimental level, The exploratory activity in the observation cage was n o t influenced by 1 gg but slightly reduced by 3 ~g ~-endorphin. The scores for socio-sexual approach towards the castrated male ,were no different from those of control animals. When an estrous female was used as a stimulus animal the 1 ~g ~-endorphin-treated males investigated the anogenital area of the female very actively and pursued her. However, only five o u t of thirteen males initiated mounting (statistically different from the controls. Fisher exact probability test, p < 0.016. The treated male repeatedly approached the female and displayed all items of the precopulatory repertoire b u t interrupted the performance just when he normally should have m o u n t e d the female. Those males who initiated mounting had a longer latency and a low m o u n t frequency compared to controls (table 1). Mounting was also performed in an abnormal way (no real clasp and thrust) so hardly any intromissions were achieved. We could see no evidence of muscular rigidity or signs of a cataleptoid state at the 1 pg dose level. On the contrary, the animals were very active. After 3 #g/~-endorphin, the frequency of pur-
192
suit decreased and after 30/~g we could confirm the cataleptoid state described by Bloom et al. (1976) and Jacquet and Marks (1976).
TABLE 1 Mounting behavior in intact male rats after intraventricular injection of ~-endorphin. Treatment
No.
Total
None 16 CSF, saline 14 ~-Endorphin 1 ~g 13 5-Endorphin 3 #g 6 Naltrexone 1 mg/kg 9 Naltrexone 1 mg/kg and -endorphin 1 ~g 8
Mounting behavior Mounting
Lattency (sec) 1
Frequency (mounts, min -l)
16 14
< 5 < 5
4.0 5.0
5
35
2.12
1
10
1.12
9
< 5
3.2
8
< 5
5.0
The effect of 1 pg/~-endorphin could be prevented by the opiate antagonist naltrexone given subcutaneously 30 min before the peptide (table 1), suggesting that the effect was induced via opiate receptors. Our data describe an effect of ~-endorphin on a behavioural pattern which is a constituent of the normal repertoire of the animal. They strengthen the hypothesis (Bloom et al., 1976), that changes in ~-lipotropin-endorphin homeostasis can cause profound behavioural changes. The ~-endorphin was purchased from Peninsula Labs, San Carlos, California, while naltrexone was donated by Endo Labs, Garden City, N.Y. The work was supported by the Swedish Medical Research Council.
References
1Median values. 2 W h e n r e t e s t e d 3 h after the ~-endorphin injection,
all animals m o u n t e d with a latency < 5 and frequency 4.5.
Bloom, F., D. Segal, N. Ling and R. Guillemin, 1976, Endorphins: profound behavioral effects in rats suggest new etiological factors in mental illness, Science 194,630. Gispen, W.H., V.M. Wiegant, A.F. Bradbury, E.C. Hulme, D.G. Smyth, C.R. Snell and De Wied, 1976, Induction of excessive grooming in the rat fragments of lipotropin, Nature 264, 794. Jacquet, Y.F. and N. Marks, 1976, The C-fragment of ~-lipotropin: An endogenous neuroleptic or antipsychotogen?, Science 194,632.
