Preweanling naltrindole administration differentially affects clonidine induced antinociception and plasma adrenaline levels in male and female neonatal rats

Abstract

1. The influence of a chronic treatment with the delta-selective opioid antagonist naltrindole (1 mg kg-1) during the preweanling period (daily injections from birth to postnatal day 19), on the antinociceptive and sympatholytic effects of the alpha2-adrenergic agonist clonidine in male and female rats of 20 and 25 days of age was investigated. 2. Nociception was assessed using the tail immersion test (water at 50 degrees C) and plasma levels of adrenaline were measured by high-performance liquid chromatography. 3. The dose of clonidine (1.5 mg kg-1) and the time point at which nociceptive responses were recorded (30 min after the administration of the drug) were chosen on the basis of dose-response (0.5, 1, 1.5 and 2 mg kg-1) and time-response (5, 10, 15, 30 and 60 min) curves which were previously carried out in naive control neonatal rats. 4. In females, the functional blockade of the delta-receptor by neonatal naltrindole treatment did not modify the sympatholytic effect of clonidine but prevented clonidine induced antinociception. Conversely, in males naltrindole treatment allowed the appearance of clonidine antinociception and the sympatholytic effect of clonidine. 5. The results indicate that the delta-receptor is involved in the modulation of antinociceptive and sympatholytic responses to clonidine in neonatal rats and suggest the existence of sex differences in the interactions between delta-opioid and alpha2-adrenergic receptors.

Figure 1

Time course of antinociceptive responses to clonidine (CLON) (0.5, 1, 1.5 and 2 mg kg⁻¹) and area under the corresponding curves over 60 min in 25-day-old naive control male and female rats, in the tail immersion test. Values represent mean±s.e.mean of 10–11 animals. Response latencies were measured 15 min before acute administration of saline (SS) or CLON (pre-treatment latencies) and 5, 10, 15, 30 and 60 min after treatment (post-treatment latencies). Student-Newman-Keuls: ^*P<0.05 vs the groups injected acutely with SS; ¶P<0.05 vs the groups injected acutely with CLON 1.5 mg kg⁻¹.

Figure 2

Effects of neonatal naltrindole treatment on antinociceptive responses to clonidine (CLON) in the tail immersion test in 20-day-old (a) and 25-day-old (b) rats. The animals were treated neonatally with saline (SS) or naltrindole (NTI) (1 mg kg⁻¹) (from birth to day 19) and subsequently studied for the acute effects of CLON (1.5 mg kg⁻¹). Histograms represent the mean±s.e.mean of 7–12 animals. Response latencies were measured 15 min before acute administration of SS or CLON (pre-treatment latencies) and 30 min after treatment (post-treatment latencies). Student-Newman-Keuls: ^*P<0.05 vs the group of the same sex treated with the same neonatal treatment and injected acutely with SS; ¶P<0.05 vs the group of the same sex treated neonatally with SS and injected acutely with CLON.

Figure 3

Effects of neonatal naltrindole treatment on plasma adrenaline levels (pg ml⁻¹) in 20-day-old (a) and 25-day-old (b) rats. The animals were treated neonatally with saline (SS) or naltrindole (NTI) (1 mg kg⁻¹) (from birth to day 19) and subsequently studied for the acute effects of clonidine (CLON) (1.5 mg kg⁻¹). Histograms represent the mean±s.e.mean of 5–7 animals. Blood samples were obtained 15 min after the completion of the tail immersion test, i.e., 45 min after acute administration of SS or CLON. Adrenaline levels were measured by high-performance liquid chromatography (HPLC). Student-Newman-Keuls: ^*P<0.05 vs the group of the same sex treated with the same neonatal treatment and injected acutely with SS; ¶P<0.05 vs the group of the same sex treated neonatally and acutely with SS.