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.

Intracellular recordings were made from neurones of the rat locus coeruleus (lc) contained within a brain slice maintained <i>in vitro</i>. When applied to the slice in known concentrations, K opioid receptor agonists produced a concentration-dependent, naloxone-reversible depression of the electrically evoked excitatory post-synaptic potential (epsp). This effect of K agonists was observed in the absence of changes in the membrane potential or input resistance of the post-synaptic cell. Similarly, the K agonists had no effect on the tetrodotoxin-resistant action potential waveform. Naloxone antagonised the response to U50488 with an apparent dissociation equilibrium constant (K<SUB>d)</SUB> of 28 nM, consistent with the response being mediated via K opioid receptors. In contrast, u opioid receptor agonists caused a membrane hyperpolarisation concomitant with a fall in neuronal input resistance, and depressed the tetrodotoxin-resistant action potential. These effects were concentration-dependent and antagonised by naloxone; the hyperpolarising action of [D-Ala<SUP>2</SUP> , NMePhe<SUP>4</SUP> , Gly-ol<SUP>5</SUP> ] enkephalin (DAGO) was antagonised by naloxone with a K<SUB>d</SUB> of 1.5 nM. These findings are in agreement with previous reports that u receptor activation increases a potassium conductance in lc neurones. The epsp was depressed, but not abolished, by the excitatory amino acid antagonists, 2-amino-5-phosphonovaleric acid (2APV) and kynurenic acid, suggesting that the epsp was at least partly mediated by an excitatory amino acid. U50488 did not depress the depolarisation produced by local application of L-glutamic acid. In addition to the epsp, a noradrenergic inhibitory post-synaptic potential (ipsp) could be evoked in lc neurones. U50488 depressed the ipsp, but this effect was not reversed by naloxone and therefore not mediated via opioid receptors. U50488 had no effect on the all or nothing depolarising potential which could be evoked in a proportion of lc neurones. The effect of U50488 on the epsp was reduced when experiments were performed in the presence of agents - either barium, quinine or 4-aminopyridine - which block potassium conductances. An <i>in vitro</i> autoradiographic study of <SUP>3</SUP> H bremazocine binding within the lc revealed that the majority of binding was displaced by a combination of unlabelled DAGO and [D-Ser<SUP>2</SUP> ] Leu enkephalin Threonine (DLSET) and so represented u sites. A significant proportion however, was displaceable by unlabelled U50488 and thus represented K binding sites. It is concluded that K opioid receptors are situated pre-synaptically within the lc and when activated depress excitatory synaptic transmission.

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