In New Zealand, it is common for young people to mix 1-benzylpiperazine (BZP) containing 'party pills' and ethanol (drinking alcohol). However, there is no scientific literature which compares the individual and combined long-term effects of these substances. Therefore, the aim of this study was to provide a comparison of BZP and ethanol's individual and combined effects on adulthood behaviour following repeated adolescent exposure. To investigate this 40 male and 40 female adolescent rats received daily exposure (post natal days 41 - 50) to BZP (10 mg/kg) and/or ethanol (2 g/kg) or saline vehicle (1 ml/kg) via intraperitoneal injection. Animals were tested in a Y maze, light/dark emergence box, and an open field during early adulthood (PND 78 - 81) and again during mid-adulthood (PND 117 - 120). Results found females treated with alcohol ambulated less in the open field. Interestingly, no other behavioural differences between the treatment groups were observed. Overall, it appeared that adolescent exposure to BZP and/or alcohol did not have long-term behavioural consequences, at least in rats. This finding was most likely due to the narrow range of testing ages adopted in the study.

In New Zealand, it is common for young people to mix 1-benzylpiperazine (BZP) containing 'party pills' and ethanol (drinking alcohol). However, there is no scientific literature which compares the individual and combined long-term effects of these substances. Therefore, the aim of this study was to provide a comparison of BZP and ethanol's individual and combined effects on adulthood behaviour following repeated adolescent exposure. To investigate this 40 male and 40 female adolescent rats received daily exposure (post natal days 41 - 50) to BZP (10 mg/kg) and/or ethanol (2 g/kg) or saline vehicle (1 ml/kg) via intraperitoneal injection. Animals were tested in a Y maze, light/dark emergence box, and an open field during early adulthood (PND 78 - 81) and again during mid-adulthood (PND 117 - 120). Results found females treated with alcohol ambulated less in the open field. Interestingly, no other behavioural differences between the treatment groups were observed. Overall, it appeared that adolescent exposure to BZP and/or alcohol did not have long-term behavioural consequences, at least in rats. This finding was most likely due to the narrow range of testing ages adopted in the study.

Increasingly, individuals in New Zealand are taking "herbal highs" with little knowledge of their possible long-term effects. Benzylpiperazine (BZP) is the predominant base drug in most herbal highs. The limited research into BZP has suggested that it produces similar effects to amphetamine, but could be 10 times less potent. There are to date, however, no long-term behavioural studies of BZP exposure. This study therefore, investigated effects of BZP exposure in adolescent male and female rats on subsequent measures of anxiety-like behaviours in adulthood. One group of experimental animals was treated daily with BZP, whereas another group received the same total amount of drug via a four day "binge" regime. The results suggested that, when observed in a Y-maze, social interaction test and a light/dark emergence test, BZP-treated rats were more anxious than control animals. In the Y-maze, male controls were more active than female controls, but BZP-treated females were more active than treated males. Results of this interaction indicate that the male rats may have been more affected by the administration of BZP during adolescence than females. Additionally, rats given the binge dose regime showed significantly increased anxiety in the Y-maze relative to the daily-exposed or control rats'. This suggests that larger quantities of BZP over a shorter time frame produce more detrimental effects than smaller quantities of BZP over a longer time frame. Overall, it would appear that the administration of BZP to adolescent animals produces behavioural changes in emotionality that are detectable in adulthood.

Increasingly, individuals in New Zealand are taking "herbal highs" with little knowledge of their possible long-term effects. Benzylpiperazine (BZP) is the predominant base drug in most herbal highs. The limited research into BZP has suggested that it produces similar effects to amphetamine, but could be 10 times less potent. There are to date, however, no long-term behavioural studies of BZP exposure. This study therefore, investigated effects of BZP exposure in adolescent male and female rats on subsequent measures of anxiety-like behaviours in adulthood. One group of experimental animals was treated daily with BZP, whereas another group received the same total amount of drug via a four day "binge" regime. The results suggested that, when observed in a Y-maze, social interaction test and a light/dark emergence test, BZP-treated rats were more anxious than control animals. In the Y-maze, male controls were more active than female controls, but BZP-treated females were more active than treated males. Results of this interaction indicate that the male rats may have been more affected by the administration of BZP during adolescence than females. Additionally, rats given the binge dose regime showed significantly increased anxiety in the Y-maze relative to the daily-exposed or control rats'. This suggests that larger quantities of BZP over a shorter time frame produce more detrimental effects than smaller quantities of BZP over a longer time frame. Overall, it would appear that the administration of BZP to adolescent animals produces behavioural changes in emotionality that are detectable in adulthood.

Violent crime and aggressive behaviour are of increasing concern in New Zealand. Much of this is displayed by adolescent males who have an association with some form of substance use, abuse or dependence. This is especially relevant for stimulant drugs, especially methamphetamine (MA), and 1-benzylpiperazine (BZP). Previous research has shown that BZP has similar neurochemical and behavioural effects to MA, and there is a large volume of research showing an association between chronic MA use and aggression. In contrast to this, there has been little research into the consequences of a single administration of MA, which is often portrayed by the media as having the same detrimental effects as chronic use. The present study was designed to determine whether or not acute MA would induce aggressive behaviour in adolescent male hooded rats. In addition, the study also examined whether BZP had a similar effect to MA. Sixty male hooded rats aged between 41 to 50 postnatal days (PND), were utilised and divided into five groups of 12 rats each: saline; 1mg/kg (low dose) or 2mg/kg (high dose) MA; 10mg/kg (low dose) or 20mg/kg (high dose) BZP. The rats were tested using the resident/intruder test of aggression, consisting of eight measures of aggressive behaviour. The results suggested that, rats treated with either a low or high dose of MA or BZP were significantly less aggressive than saline-treated rats. There appeared to be little to distinguish between the two drugs in their effects on the responses recorded. It was concluded that an acute administration of either MA or BZP did not increase aggression, and thus did not support the view that aggression will result from a single dose of MA (or indeed BZP that has not been previously investigated in this context).

In the last few years, the prevalence of legal party pills in New Zealand has risen dramatically. These pills contain new piperazine designer drugs, two of the more common being 1-benzylpiperazine (BZP) and m-trifluoromethylphenylpiperazine (TFMPP). This thesis describes an optimised LC-MS/MS method for the detection of BZP and TFMPP in whole blood, using an automated solid phase extraction (SPE) for sample clean-up. The method was validated on three different days using five replicate samples each day. The standard curve was linear from 7 - 7000 ng/mL for BZP and 10 - 10,000 ng/mL for TFMPP, with coefficients of variation (CV) below 10%, and accuracy greater than 90% for both drugs. The method was used to quantitate samples provided by the Medical Research Institute of New Zealand. Blood levels were used to show concentrations in the blood over time, and relate these to performance of subjects on a driving simulator. The study was stopped after 41% of the participants who received BZP and TFMPP had adverse reactions to the pills, including vomiting and migraines. The LC-MS/MS method was also used to detect and quantitate methamphetamine, amphetamine, methylenedioxymethamphetamine, methylenedioxyamphetamine, morphine, codeine and 6-monoacetylmorphine in hair. The drugs were extracted from 20 mg of hair using hydrochloric acid in a water bath overnight, then purified using SPE. Validation on three days with five replicate samples gave coefficients of variation (CV) below 12% and acceptable accuracy for all drugs. The method was tested on three samples, previously reported by Environmental Science and Research (ESR) using gas chromatography mass spectrometry (GC-MS) giving results in good agreement. This thesis describes a sensitive, accurate, reproducible LC-MS/MS method easily adapted to analyse drugs of abuse in different biological matrices. It demonstrates the versatility of LC-MS/MS and its applications in forensic work.

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