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Naltrexone blocks nicotine-induced prolactin release
0028-3908/89 $3.00+0.00 Pergamon Press plc
Neuropharmacology Vo1.28, No.11, pp.1287-1290, 1989 Printed in Great Britain
NALTREXONE
PROLAC’MN RELEASE
BLOCKS NICOTINE-INDUCED
C.M. Flores, B.A. Hulihan-Giblin and K.J. Kellar Department of Pharmacology, Georgetown University Medical Center Washington, D.C. 20007
(Accepted
26
August
1989)
Summary--Two receptor populations involved in the release of prolactin were examined in conscious, freely moving, male rats bearing indwelling jugular cannulae. The intravenous admin&ztion of either nicotine or morphine increased plasma prolactin levels. Pretreatment with the nicotinic antagonist mecamylamine blocked the prolactin response to nicotine only. In contrast, the opiate antagonist naltrexone blocked the prolactin response to both nicotine and morphine. These findings indicate that the nicotine stimulated release of prolactin is dependent not only on functional nicotinic cholinergic receptors but on opiate receptors as welt! This su&ests that nicotine and morphine release prolactin via a common pathway containing nicotinic cholinergic and opiate synapses in series.
Key words--prolactin
regulation,
pathway, morphine,
mecamylamine
Nicotine (Andersson, Eneroth and Agnati, 1981; Sharp and Beyer, 1986) and morphine (Grandison and Guidotti, 1977; Spiegel, Kourides and Pasternak, 1982; Koenig, Mayfield, McCann and Krulich, 1984) stimulate prolactin release, in vivo. However, the functional relationship between the neural elements activated by these drugs is not known. Thus, the purpose of the present studies was to determine if nicotine and morphine utilize a common pathway to release prolactin and, if so, to establish the serial order of the involved receptors.
METHODS
Animals Male, Sprague-Dawley rats (Zivic-Miller), weighing 350-450 gm were group housed in a temperature light controlled room (23’ C.; lights on 7:OOA.M. to 7:00 P.M.) with food and water, ad libitum.
and
Jugular vein cannulation Twenty-four hours preceding the experiment, rats were anesthetized with pentobarbital (45 mg/kg), and a cannula was inserted into the jugular vein according to a previously described procedure (Harms and Ojeda, 1974). The cannulae were filled with heparinized saline (500 units/ml) and closed with a knot. Experimental Procedure All experiments were carried out between 10:00 A.M. and 2:00 P.M. On the morning of the experiment, food and water were removed from each cage. Each cannula was cut and attached via a segment of 23gauge stainless steel tubing to a 38 cm length of PE-50 tubing connected to a 1 cc syringe. The tubing and syringe were passed through the wire cage cover and allowed to hang outside of the cage so as not to disturb the animals during blood withdrawal or drug injection. Following a period of acclimation, baseline blood samples were drawn and rats were then pretreated with either isotonic saline, mecamylamine HCl (3 mg/kg) or naltrexone HCl (4 mg/kg). After each drug injection (200 ~1) the cannula was flushed with an equal volume of saline to insure full delivery of drug. Sixty min later blood samples were again taken, and each rat was successively administered nicotine bitartrate dihydrate (100 pg/kg; equivalent to 33 fig/kg of nicotine free base) and morphine sulfate (3 mg/kg) with 30 min intervals between each injection. Beginning two min after administration of each drug and periodically for the following 30 min, timed blood samples were collected into 1.5 ml tubes, centrifuged and frozen at -20” C. Following each blood collection (200 nl), an equal volume of saline was injected to maintain blood volume.
1287
1288
Preliminary
Notes
Prolactin Assay Plasma aliouots were analvzed for immunoreactive nrolactin levels by radioimmunoassay using a double antibody method and rat pro&tin reference standards (RP-3) supplied by-the National Hormone and Pituitary Program of the NIDDK. The inter- and intra-assay coefficients of variation differed by less than 10 % and the sensitivity of the assay was 0.12 ng/tube. Analysk of data Baseline measurements of plasma prolactin concentrations were made in blood collected immediately before each drug injection. Peak plasma prolactin concentrations were determined from blood samples collected periodically for 30 min after each drug injection. Statistical comparisons between two means were made by ANOVA followed by Newman-Keuls test. A p-value of 0.05 or less was considered statistically significant. Drugs Mecamylamine HCl (kindly provided by Merck, Sharp and Dohme Research Laboratories; Rahway, NJ.), naltrexone HCI (kindly provided by the National Institute on Drug Abuse; Rockville, MD), nicotine bitartrate dihydrate (ICN Pharmaceuticals, Plainview, N.Y.), morphine sulfate (Mallinckdodt, St. Louis, MO) and TRH (Bachem Inc., Torrance, CA) were dissolved in isotonic saline.
RESULTS In rats pretreated with saline, an i.v. injection of nicotine bitartrate (100 pg/kg) increased the plasma prolactin concentration from a baseline value of 8.3 ng/ml to a peak value of 33.4 ng/ml (Fig. 1A). The prolactin concentration returned to baseline values within 30 min after injection of nicotine, and at that time morphine sulphate (3 mg/kg) was injected. Morphine increased the plasma prolactin concentration to a peak value of 67.7 “g/ml (Fig. 1A). In rats pretreated with mecamylamine (3 mg/kg), nicotine increased prolactin concentrations from a baseline value of 7.2 ng/ml to a peak value of just 11.7 ng/ml (Fig. 1B). Thus, mecamylamine almost completely blocked nicotine-induced prolactin release. In contrast, mecamylamine pretreatment did not significantly alter the morphine-induced release of prolactin, which rose from a baseline value of 8.7 ng/ml to a peak stimulated value of 49.5 ng/ml (Fig. 1B).
B
A
l
h
Figure 1. Peak plasma prolactin levels in response to i.v. nicotine (100 pg/kg) and morphine (3 mg/kg) in (A) saline (n=4) and (B) mecamylamine (n=6) pretreated rats. Results are expressed as mean f SEM plasma prolactin levels (ng/ml). Hatched bars represent baseline values and open bars peak stimulated values. *Differs significantly from baseline **Differs significantly from value (p 5 0.01). response in saline pretreated rats (p < 0.01).
I,
NIC
h IOR
In a second experiment, the effects of the opiate receptor antagonist, naltrexone, on prolactin release induced by nicotine and morphine were measured. As compared to rats pretreated with saline, there appears to be a slight decrease in the baseline prolactin values of rats pretreated with naltrexone. While this trend did not reach statistical significance, it is consistent with the findings of other investigators (Grandison and Guidotti, 1977; Bruni, Van Vugt, Marshall and Meites, 1977). In saline pretreated rats, the characteristic increases in plasma prolactin concentrations following nicotine and morphine were observed (Fig. 2A). As expected, pretreatment with naltrexone (4 mg/kg) completely blocked morphine-induced prolactin release (Fig. 2B). Moreover, naltrexone pretreatment significantly attenuated (p < 0.01) nicotine-induced prolactin release, with prolactin concentrations rising to a peak value of only 11.0 ng/ml as opposed to 39.4 ng/ml in the saline pretreated rats (Fig. 2B).
Preliminary Notes
1289
Figure 2. Peak plasma prolactin levels in response to i.v. nicotine (lOOug/kg) and morphine (3 mg/kg) in (A) saline (n=9) and (B) naltrexone (n=8) pretreated rats. Results are expressed as mean f SEM plasma prolactin levels (ng/ml). Hatched bars represent baseline values and open bars peak *Differs significantly from stimulated values. baseline value (p 5 0.01). **Differs significantly from response in salline pretreated rats (p 50.01).
0-
NIC HOR
NIC
HOR
DISCUSSION The release of prolactin by nicotine and morphine is mediated, respectively, by a neuronal nicotinic cholinergic receptor (Sharp and Beyer, 1986) and an opiate receptor (Spiegel, et al., 1982; Koenig, et al., 1984). The EC for prolactin release by the intravenous administration of nicotine bitartrate is approximately 100 Lte/ke (Hu Pthan-Giblin. Lumokin and Kellar. in Dress). while that for morohine sulfate is aouroximatelv 5 mg/kg (Spiegel, et al., 1982). ‘n-endorphin appeals to be the most potent kndogenous opio% peptide in releasing prolactin (Rivier, Vale, Ling, Brown and Guillemin, 1977). The present results indicate that the nicotine-induced release of prolactin is dependent on functional opiate receptors as well as on nicotinic cholinergic receptors. An alternative explanation for these results could be that naltrexone blocks nicotinic receptors as well as opiate receptors; however, in competition studies in vitro, naltrexone does not compete effectively for nicotinic cholinergic binding sites labeled by [3H]acetylcholine (unpublished data). The response to thyrotropin releasing hormone (2 bg/kg) was unaffected by naltrexone pretreatment (data not shown), indicating that naltrexone does not deplete releasable pools of prolactin or non-specifically inhibit prolactin release. Thus, the simplest explanation for the results presented here is that a synapse containing opiate receptors is in series with and downstream from a synapse containing nicotinic cholinergic receptors in a neural pathway controlling prolactin release. The release of prolactin by opiates in the rat has been shown to be dependent on intact serotonergic neurotransmission (Spampinato, Locatelli, Cocchi, Vicentini, Bajusa, Ferri and Muller, 1979; Koenig, Mayfield, McCann and Krulich, 1979; Bero and Kuhn, 1986a and 1986b). Taken together with that observation, the present results suggest that nicotinic cholinergic agonists, opiate agonists and serotonergic agonists release prolactin through a common neuronal pathway. Moreover, preliminary results indicate that pretreatment with the serotonergic antagonist, methysergide, blocks not only serotonin agonist-induced release of prolactin but nicotine- and morphine-induced release as well (Flores, et al., unpublished data). Additional studies will be required to determine whether activation of this pathway releases prolactin through inhibition of dopamine, the prolactin inhibitory factor, or through an as yet unidentified mechanism. .I,
w.
ACKNOWLEDGEMENTS The authors thank S. Renee Wheeler and Lisa R. West-Johnsrud for their expert technical assistance and Dr. Michael D. Lumpkin for his generous assistance and his expert advice. This work was supported 86-100).
by a grant from the Alzheimer’s Disease and Related Disorders Association
(II-
1290
Preliminary
Notes
REFERENCES Andersson, K., Eneroth, P., and Agnati, L.F. (1981) Nicotine-induced increases of noradrenalin turnover in discrete noradrenalin nerve terminal systems of the hypothalamus and median eminence of the rat and their relationship to changes in the secretion of adenohypophyseal hormones. Acru Physior Scud 113:227231. Bero, LA. and Kuhn, CM. (1986a) Differential ontogeny of opioid, dopaminergic of prolactin secretion. .I. PharmucoL Exp. Thu. 240: 825830. Bero, L.A. and antinociception
Kuhn, C.M. (1986b) Role of serotonin in opiate-induced in the developing rat. J. PhamacoL Exp. Ther. 240: 831-836.
and serotonergic
prolactin
regulation
secretion
and
Bruni, J.F., Van Vugt, D., Marshall, S. and Meites, J. (1977) Effects of naloxone, morphine and methionine enkephalin on serum prolactin, htteinizing hormone, follicle stimulating hormone, thyroid stimulating hormone and growth hormone. Life Sci 21: 461-466. Grandison, A. and Guidotti, A. (1977) Regulation 357-359.
of prolactin release by endogenous
opiates. Nature. 270:
Hulihan-Giblin, B.A., Lumpkin, M.D. and Kellar, K.J. (in press) Acute effects of nicotine on prolactin release in the rat: Agonist and antagonist effects of a single injection of nicotine. J. PhamacoL Exp. Ther. Koenig, J.I., May-field, M.A., McCann, SM. and Krulich, L. (1979) Stimulation morphine: Role of the central serotonergic system. Life Sci. 25: 853-864.
of prolactin
secretion
by
Koenig, J.I., Mayfield, M.A., McCann, S.M. and Krulich, L. (1984) Differential role of the opioid cc and 6 receptors in the activation of prolactin and growth hormone secretion in the male rat. Life Sci. 34: 18291837. Harms, P.G. and Ojeda, S.R. (1974) A rapid and simple procedure vein. J. AppL PhysioL 36: 391-392.
for chronic cannulation
Rivier, C., Vale, W., Ling, N., Brown, M. and Guillemin, R. (1977) Stimulation prolactin and growth hormone by B-endorphin. Endocrinol. 100: 238-241.
of the rat jugular
in viva of the secretion
of
Sharp, B.M. and Beyer, H.S. (1986) Rapid desensitization of the acute stimulatory effects of nicotine on rat plasma adrenocorticotropin and prolactin. J. PhurmacoL Exp. Ther. 238: 486-491. Spampinato, S., Locatelli, V., Cocchi, D., Vicentini, L., Bajusz, S., Ferri, S. and Muller, E. (1979) Involvement of brain serotonin in the prolactin-releasing effect of opioid peptides. Endocrinol. 105: 163-170. Spiegel, K., Kourides, LA. and Pasternak, G.W. (1982) Prolactin and growth hormone in the rat: Different receptor mechanisms. Science 217: 745747.
release by morphine
Neuropharmacology Vo1.28, No.11, pp.1287-1290, 1989 Printed in Great Britain
NALTREXONE
PROLAC’MN RELEASE
BLOCKS NICOTINE-INDUCED
C.M. Flores, B.A. Hulihan-Giblin and K.J. Kellar Department of Pharmacology, Georgetown University Medical Center Washington, D.C. 20007
(Accepted
26
August
1989)
Summary--Two receptor populations involved in the release of prolactin were examined in conscious, freely moving, male rats bearing indwelling jugular cannulae. The intravenous admin&ztion of either nicotine or morphine increased plasma prolactin levels. Pretreatment with the nicotinic antagonist mecamylamine blocked the prolactin response to nicotine only. In contrast, the opiate antagonist naltrexone blocked the prolactin response to both nicotine and morphine. These findings indicate that the nicotine stimulated release of prolactin is dependent not only on functional nicotinic cholinergic receptors but on opiate receptors as welt! This su&ests that nicotine and morphine release prolactin via a common pathway containing nicotinic cholinergic and opiate synapses in series.
Key words--prolactin
regulation,
pathway, morphine,
mecamylamine
Nicotine (Andersson, Eneroth and Agnati, 1981; Sharp and Beyer, 1986) and morphine (Grandison and Guidotti, 1977; Spiegel, Kourides and Pasternak, 1982; Koenig, Mayfield, McCann and Krulich, 1984) stimulate prolactin release, in vivo. However, the functional relationship between the neural elements activated by these drugs is not known. Thus, the purpose of the present studies was to determine if nicotine and morphine utilize a common pathway to release prolactin and, if so, to establish the serial order of the involved receptors.
METHODS
Animals Male, Sprague-Dawley rats (Zivic-Miller), weighing 350-450 gm were group housed in a temperature light controlled room (23’ C.; lights on 7:OOA.M. to 7:00 P.M.) with food and water, ad libitum.
and
Jugular vein cannulation Twenty-four hours preceding the experiment, rats were anesthetized with pentobarbital (45 mg/kg), and a cannula was inserted into the jugular vein according to a previously described procedure (Harms and Ojeda, 1974). The cannulae were filled with heparinized saline (500 units/ml) and closed with a knot. Experimental Procedure All experiments were carried out between 10:00 A.M. and 2:00 P.M. On the morning of the experiment, food and water were removed from each cage. Each cannula was cut and attached via a segment of 23gauge stainless steel tubing to a 38 cm length of PE-50 tubing connected to a 1 cc syringe. The tubing and syringe were passed through the wire cage cover and allowed to hang outside of the cage so as not to disturb the animals during blood withdrawal or drug injection. Following a period of acclimation, baseline blood samples were drawn and rats were then pretreated with either isotonic saline, mecamylamine HCl (3 mg/kg) or naltrexone HCl (4 mg/kg). After each drug injection (200 ~1) the cannula was flushed with an equal volume of saline to insure full delivery of drug. Sixty min later blood samples were again taken, and each rat was successively administered nicotine bitartrate dihydrate (100 pg/kg; equivalent to 33 fig/kg of nicotine free base) and morphine sulfate (3 mg/kg) with 30 min intervals between each injection. Beginning two min after administration of each drug and periodically for the following 30 min, timed blood samples were collected into 1.5 ml tubes, centrifuged and frozen at -20” C. Following each blood collection (200 nl), an equal volume of saline was injected to maintain blood volume.
1287
1288
Preliminary
Notes
Prolactin Assay Plasma aliouots were analvzed for immunoreactive nrolactin levels by radioimmunoassay using a double antibody method and rat pro&tin reference standards (RP-3) supplied by-the National Hormone and Pituitary Program of the NIDDK. The inter- and intra-assay coefficients of variation differed by less than 10 % and the sensitivity of the assay was 0.12 ng/tube. Analysk of data Baseline measurements of plasma prolactin concentrations were made in blood collected immediately before each drug injection. Peak plasma prolactin concentrations were determined from blood samples collected periodically for 30 min after each drug injection. Statistical comparisons between two means were made by ANOVA followed by Newman-Keuls test. A p-value of 0.05 or less was considered statistically significant. Drugs Mecamylamine HCl (kindly provided by Merck, Sharp and Dohme Research Laboratories; Rahway, NJ.), naltrexone HCI (kindly provided by the National Institute on Drug Abuse; Rockville, MD), nicotine bitartrate dihydrate (ICN Pharmaceuticals, Plainview, N.Y.), morphine sulfate (Mallinckdodt, St. Louis, MO) and TRH (Bachem Inc., Torrance, CA) were dissolved in isotonic saline.
RESULTS In rats pretreated with saline, an i.v. injection of nicotine bitartrate (100 pg/kg) increased the plasma prolactin concentration from a baseline value of 8.3 ng/ml to a peak value of 33.4 ng/ml (Fig. 1A). The prolactin concentration returned to baseline values within 30 min after injection of nicotine, and at that time morphine sulphate (3 mg/kg) was injected. Morphine increased the plasma prolactin concentration to a peak value of 67.7 “g/ml (Fig. 1A). In rats pretreated with mecamylamine (3 mg/kg), nicotine increased prolactin concentrations from a baseline value of 7.2 ng/ml to a peak value of just 11.7 ng/ml (Fig. 1B). Thus, mecamylamine almost completely blocked nicotine-induced prolactin release. In contrast, mecamylamine pretreatment did not significantly alter the morphine-induced release of prolactin, which rose from a baseline value of 8.7 ng/ml to a peak stimulated value of 49.5 ng/ml (Fig. 1B).
B
A
l
h
Figure 1. Peak plasma prolactin levels in response to i.v. nicotine (100 pg/kg) and morphine (3 mg/kg) in (A) saline (n=4) and (B) mecamylamine (n=6) pretreated rats. Results are expressed as mean f SEM plasma prolactin levels (ng/ml). Hatched bars represent baseline values and open bars peak stimulated values. *Differs significantly from baseline **Differs significantly from value (p 5 0.01). response in saline pretreated rats (p < 0.01).
I,
NIC
h IOR
In a second experiment, the effects of the opiate receptor antagonist, naltrexone, on prolactin release induced by nicotine and morphine were measured. As compared to rats pretreated with saline, there appears to be a slight decrease in the baseline prolactin values of rats pretreated with naltrexone. While this trend did not reach statistical significance, it is consistent with the findings of other investigators (Grandison and Guidotti, 1977; Bruni, Van Vugt, Marshall and Meites, 1977). In saline pretreated rats, the characteristic increases in plasma prolactin concentrations following nicotine and morphine were observed (Fig. 2A). As expected, pretreatment with naltrexone (4 mg/kg) completely blocked morphine-induced prolactin release (Fig. 2B). Moreover, naltrexone pretreatment significantly attenuated (p < 0.01) nicotine-induced prolactin release, with prolactin concentrations rising to a peak value of only 11.0 ng/ml as opposed to 39.4 ng/ml in the saline pretreated rats (Fig. 2B).
Preliminary Notes
1289
Figure 2. Peak plasma prolactin levels in response to i.v. nicotine (lOOug/kg) and morphine (3 mg/kg) in (A) saline (n=9) and (B) naltrexone (n=8) pretreated rats. Results are expressed as mean f SEM plasma prolactin levels (ng/ml). Hatched bars represent baseline values and open bars peak *Differs significantly from stimulated values. baseline value (p 5 0.01). **Differs significantly from response in salline pretreated rats (p 50.01).
0-
NIC HOR
NIC
HOR
DISCUSSION The release of prolactin by nicotine and morphine is mediated, respectively, by a neuronal nicotinic cholinergic receptor (Sharp and Beyer, 1986) and an opiate receptor (Spiegel, et al., 1982; Koenig, et al., 1984). The EC for prolactin release by the intravenous administration of nicotine bitartrate is approximately 100 Lte/ke (Hu Pthan-Giblin. Lumokin and Kellar. in Dress). while that for morohine sulfate is aouroximatelv 5 mg/kg (Spiegel, et al., 1982). ‘n-endorphin appeals to be the most potent kndogenous opio% peptide in releasing prolactin (Rivier, Vale, Ling, Brown and Guillemin, 1977). The present results indicate that the nicotine-induced release of prolactin is dependent on functional opiate receptors as well as on nicotinic cholinergic receptors. An alternative explanation for these results could be that naltrexone blocks nicotinic receptors as well as opiate receptors; however, in competition studies in vitro, naltrexone does not compete effectively for nicotinic cholinergic binding sites labeled by [3H]acetylcholine (unpublished data). The response to thyrotropin releasing hormone (2 bg/kg) was unaffected by naltrexone pretreatment (data not shown), indicating that naltrexone does not deplete releasable pools of prolactin or non-specifically inhibit prolactin release. Thus, the simplest explanation for the results presented here is that a synapse containing opiate receptors is in series with and downstream from a synapse containing nicotinic cholinergic receptors in a neural pathway controlling prolactin release. The release of prolactin by opiates in the rat has been shown to be dependent on intact serotonergic neurotransmission (Spampinato, Locatelli, Cocchi, Vicentini, Bajusa, Ferri and Muller, 1979; Koenig, Mayfield, McCann and Krulich, 1979; Bero and Kuhn, 1986a and 1986b). Taken together with that observation, the present results suggest that nicotinic cholinergic agonists, opiate agonists and serotonergic agonists release prolactin through a common neuronal pathway. Moreover, preliminary results indicate that pretreatment with the serotonergic antagonist, methysergide, blocks not only serotonin agonist-induced release of prolactin but nicotine- and morphine-induced release as well (Flores, et al., unpublished data). Additional studies will be required to determine whether activation of this pathway releases prolactin through inhibition of dopamine, the prolactin inhibitory factor, or through an as yet unidentified mechanism. .I,
w.
ACKNOWLEDGEMENTS The authors thank S. Renee Wheeler and Lisa R. West-Johnsrud for their expert technical assistance and Dr. Michael D. Lumpkin for his generous assistance and his expert advice. This work was supported 86-100).
by a grant from the Alzheimer’s Disease and Related Disorders Association
(II-
1290
Preliminary
Notes
REFERENCES Andersson, K., Eneroth, P., and Agnati, L.F. (1981) Nicotine-induced increases of noradrenalin turnover in discrete noradrenalin nerve terminal systems of the hypothalamus and median eminence of the rat and their relationship to changes in the secretion of adenohypophyseal hormones. Acru Physior Scud 113:227231. Bero, LA. and Kuhn, CM. (1986a) Differential ontogeny of opioid, dopaminergic of prolactin secretion. .I. PharmucoL Exp. Thu. 240: 825830. Bero, L.A. and antinociception
Kuhn, C.M. (1986b) Role of serotonin in opiate-induced in the developing rat. J. PhamacoL Exp. Ther. 240: 831-836.
and serotonergic
prolactin
regulation
secretion
and
Bruni, J.F., Van Vugt, D., Marshall, S. and Meites, J. (1977) Effects of naloxone, morphine and methionine enkephalin on serum prolactin, htteinizing hormone, follicle stimulating hormone, thyroid stimulating hormone and growth hormone. Life Sci 21: 461-466. Grandison, A. and Guidotti, A. (1977) Regulation 357-359.
of prolactin release by endogenous
opiates. Nature. 270:
Hulihan-Giblin, B.A., Lumpkin, M.D. and Kellar, K.J. (in press) Acute effects of nicotine on prolactin release in the rat: Agonist and antagonist effects of a single injection of nicotine. J. PhamacoL Exp. Ther. Koenig, J.I., May-field, M.A., McCann, SM. and Krulich, L. (1979) Stimulation morphine: Role of the central serotonergic system. Life Sci. 25: 853-864.
of prolactin
secretion
by
Koenig, J.I., Mayfield, M.A., McCann, S.M. and Krulich, L. (1984) Differential role of the opioid cc and 6 receptors in the activation of prolactin and growth hormone secretion in the male rat. Life Sci. 34: 18291837. Harms, P.G. and Ojeda, S.R. (1974) A rapid and simple procedure vein. J. AppL PhysioL 36: 391-392.
for chronic cannulation
Rivier, C., Vale, W., Ling, N., Brown, M. and Guillemin, R. (1977) Stimulation prolactin and growth hormone by B-endorphin. Endocrinol. 100: 238-241.
of the rat jugular
in viva of the secretion
of
Sharp, B.M. and Beyer, H.S. (1986) Rapid desensitization of the acute stimulatory effects of nicotine on rat plasma adrenocorticotropin and prolactin. J. PhurmacoL Exp. Ther. 238: 486-491. Spampinato, S., Locatelli, V., Cocchi, D., Vicentini, L., Bajusz, S., Ferri, S. and Muller, E. (1979) Involvement of brain serotonin in the prolactin-releasing effect of opioid peptides. Endocrinol. 105: 163-170. Spiegel, K., Kourides, LA. and Pasternak, G.W. (1982) Prolactin and growth hormone in the rat: Different receptor mechanisms. Science 217: 745747.
release by morphine