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J K Rowlett

Publications and source records attributed to J K Rowlett.

59 records · Page 4Linked to original sources

Effects of repeated apomorphine and haloperidol treatments on subsequent behavioral sensitivity to apomorphine.

In a 2 x 2 factorial design, four groups of rats (n = 10 each) were injected daily with haloperidol (0.5 mg/kg IP) or its injection vehicle and apomorphine (1.0 mg/kg SC) or its vehicle for 21 consecutive days. Then, following a six-day drug-free rest interval, all rats were tested for locomotor activity in photocell arenas after an apomorphine injection on four additional days. Major findings were as follows: (a) rats pretreated with apomorphine were significantly more active following an apomorphine injection than rats pretreated with vehicle; (b) the development of sensitization to apomorphine was completely blocked by the concurrent administration of haloperidol during the pretreatment phase; and (c) pretreatment of rats with haloperidol alone did not affect subsequent sensitivity to apomorphine. These results suggest that the development of behavioral sensitization to apomorphine is related specifically to the stimulation of dopamine receptors.

Animals↗

Environmental enrichment attenuates locomotor sensitization, but not in vitro dopamine release, induced by amphetamine.

Rats were raised from weanling until young adulthood in either an enriched condition (EC) or isolated condition (IC). Following this, the locomotor and rewarding effects of amphetamine were determined using the conditioned place preference (CPP) paradigm. EC rats were more sensitive to the acute locomotor stimulant effect and rewarding effect of amphetamine relative to IC rats. In contrast, EC rats were less sensitive than IC rats to the locomotor sensitization effect obtained across repeated amphetamine injections. To determine the effect of environmental enrichment on alteration of brain dopamine (DA) function induced by amphetamine, the effect of amphetamine on electrically evoked release of DA and dihydroxyphenylacetic acid (DOPAC) was determined in vitro using tissue slices from the nucleus accumbens and striatum of EC and IC rats. No differences between EC and IC rats in release of DA or DOPAC were evident, suggesting that the environmentally induced difference in sensitivity to the behavioral effects of amphetamine involves a neural mechanism extrinsic to the mesolimbic and nigrostriatal terminal field regions.

3,4-Dihydroxyphenylacetic Acid↗

Impaired supersensitivity to morphine following chronic naltrexone treatment in senescent rats.

Chronic administration of opiate antagonists produces an increase in the density of opiate receptors, as well as an enhanced sensitivity to the analgesic and locomotor depressant effects of morphine. The present study assessed whether aging alters these regulatory processes. Young (3-4 months), middle-aged (10-11 months), and senescent (25-30 months) rats were implanted subdermally with slow-release naltrexone pellets or were given sham surgery. The pellets were removed 10 days later. Twenty-four hours after pellet removal, morphine-induced (5 mg/kg, SC) analgesia and locomotor activity were assessed. Young and middle-aged rats treated with naltrexone showed enhanced sensitivity to the analgesic and locomotor activity depressant effects of morphine relative to age-matched controls. In contrast, senescent rats treated with naltrexone did not differ from age-matched controls in their response to morphine. The density of opiate receptors labeled with 3H-naloxone was measured in the anterior striatum. Both young and senescent rats treated with naltrexone exhibited an increase in opiate receptor density relative to age-matched controls. The results indicate that senescent rats are capable of up-regulating opiate receptors following chronic naltrexone treatment but do not exhibit the corresponding functional supersensitivity to morphine.

Aging↗

Locomotor activity and dopamine synthesis following 1 and 15 days of withdrawal from repeated apomorphine treatments.

In two experiments, the effects of repeated apomorphine treatments on locomotor activity and terminal field dopamine synthesis was assessed after either a 1- or 15-day withdrawal period. In the first experiment, rats (n = 11/group) were treated with apomorphine (1.0 mg/kg, s.e.) or vehicle and tested for locomotor activity daily for 10 days. Fifteen days after the last repeated treatment, all rats received 1.0 mg/kg apomorphine and were tested for locomotor activity. Locomotor sensitization developed over the 10 day period and was still evident after the 15-day withdrawal period. In the second experiment rats (n = 11/group) were treated with apomorphine (1.0 mg/kg, s.c.) or vehicle and tested for locomotor activity daily for 10 days. Dopamine synthesis was assessed following 1 or 15 days of withdrawal by measuring dihydroxyphenylalanine (DOPA) accumulation (after DOPA decarboxylase inhibition with NSD-1015) in striatum and nucleus accumbens-olfactory tuberele. As in the first experiment, rats treated with repeated apomorphine showed locomotor sensitization over the 10 days, relative to controls. Dopamine synthesis was reliably enhanced in the striatum, but not nucleus accumbens-olfactory tuberele, following both 1- and 15-day withdrawal periods. These results indicate that enhanced basal dopamine synthesis following repeated apomorphine treatments, similar to locomotor sensitization, is a persistent phenomenon.

Animals↗